Metathesis catalysts and methods thereof

ABSTRACT

The present invention provides, among other things, novel compounds and methods for metathesis reactions. In some embodiments, a provided compound has the structure of formula I or II. In some embodiments, the present invention provides compounds and methods for Z-selective olefin metathesis.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority to U.S. Provisional ApplicationSer. No. 61/813,096, filed Apr. 17, 2013, the entirety of which isincorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under Grant Nos.CHE1111133 and CHE1205189 awarded by the National Science Foundation.The government has certain rights in the invention.

FIELD OF THE INVENTION

The present invention generally relates to metathesis reactions.

BACKGROUND

Catalytic olefin metathesis has transformed chemical synthesis andoffers exceptionally efficient pathways for synthesis of alkenes. In thelast several years sterically demanding phenoxide ligands have beenemployed to make Mo- and W-based MAP (MonoAlkoxide Pyrrolide) catalystsfor olefin metathesis reactions. One of the first was OBr₂Bitet, anenantiomerically pure monophenoxide ligand that yielded diastereomericmixtures of MAP catalysts (R′=H or Me) for enantioselectivering-opening/cross-metathesis reactions (Ibrahem, I; Yu, M.; Schrock, R.R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 3844).

In the process, it was found that the reaction was not onlyenantioselective but also Z-selective. The search for other suitablesterically demanding phenoxides led to terphenoxides such asO-2,6-(2,4,6-i-Pr₃C₆H₂)₂C₆H₃ (OHIPT)(Stanciu, C.; Olmstead, M. M.;Phillips, A. D.; Stender, M.; Power, P. P. Eur. J. Inorg. Chem. 2003,3495) and O-2,6-Mesityl₂C₆H₃ (OHMT) (Dickie, D. A.; MacIntosh, I. S.;Ino, D. D.; He, Q.; Labeodan, O. A.; Jennings, M. C.; Schatte, G.;Walsby, C. J.; Clyburne, J. A. C. Can. J. Chem. 2008, 86, 20), whichwere employed to produce Z-selective catalysts for ROMP ((a) Flook, M.M.; Jiang, A. J.; Schrock, R. R.; Müller, P.; Hoveyda, A. H. J. Am.Chem. Soc. 2009, 131, 7962. (b) Flook, M. M.; Gerber, L. C. H.;Debelouchina, G. T.; Schrock, R. R. Macromolecules 2010, 43, 7515) andhomocoupling of terminal olefins ((a) Jiang, A. J.; Zhao, Y.; Schrock,R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 16630. (b) Marinescu,S. C.; Schrock, R. R.; Müller, P.; Takase, M. K.; Hoveyda, A. H.Organometallics 2011, 30, 1780). Decafluoroterphenoxide(O-2,6-(C₆F₅)₂C₆H₃=ODFT) has also been added to the list of2,6-terphenoxides (Yuan, J.; Schrock, R. R.; Müller, P.; Axtell, J. C.;Dobereiner, G. E. Organometallics 2012, 31, 4650). Recently it also hasbeen possible to make bisaryloxide complexes that are especiallyefficient in certain stereoselective reactions, one example beingMo(NC₆F₅)(CHCMe₂Ph)(OF₂Bitet)₂, where OF₂Bitet is a fluorinated relativeof OBr₂Bitet (Wang, C.; Haeffner, F.; Schrock, R. R.; Hoveyda, A. H.Angew. Chem. Int. Ed. 2013, 52, 1939). Despite all the development,there remains a need for olefin metathesis catalysts and methods forhighly selective and efficient synthesis of Z alkenes.

SUMMARY

The present invention, among other things, encompasses the recognitionthat new catalysts and methods for highly efficient Z-selectivemetathesis reactions are needed. In some embodiments, the presentinvention provides new compounds as sterically demanding ligands orligand precursors suitable for preparation of compounds that promoteZ-selective metathesis reactions. In some embodiments, a new stericallydemanding ligand is an aryloxide ligand. In some embodiments, thepresent invention provides new compounds that promote metathesisreactions. In some embodiments, a provided compound comprises a newsterically demanding ligand. In some embodiments, a provided compoundcomprises a new sterically demanding aryloxide ligand. In someembodiments, a provided compound is a MAP compound comprising a newsterically demanding aryloxide ligand. In some embodiments, the presentinvention provides new methods for metathesis reactions. In someembodiments, a provided method produces Z-alkenes with unprecedentedefficiency and/or selectivity.

In some embodiments, the present invention provides a compound offormula I:

wherein:

-   M is molybdenum or tungsten;-   R¹ is an optionally substituted group selected from C₁₋₂₀ aliphatic,    C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms independently selected    from nitrogen, oxygen, or sulfur, phenyl, a 3-7 membered saturated    or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur;-   each of R² and R³ is independently R′, —OR′, —SR′, —N(R′)₂,    —OC(O)R′, —SOR′, —SO₂R′, —SO₂N(R′)₂, —C(O)N(R′)₂, —NR′C(O)R′, or    —NR′SO₂R′;-   m is 0-3;-   Ring B is an optionally substituted group selected from phenyl or a    5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms    independently selected from nitrogen, oxygen, or sulfur;-   each of p and q is independently 0-4;-   each of Ring C and Ring D is independently an optionally substituted    5-membered monocyclic heteroaryl ring having 1-4 nitrogen atoms;-   each of R^(x), R^(y) and R^(z) is independently halogen, —OR′,    —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)₂, —NR′SO₂R′,    —NR′SO₂N(R′)₂, —NR′OR′, or an optionally substituted group selected    from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, phenyl, a    3-7 membered saturated or partially unsaturated carbocyclic ring, an    8-10 membered bicyclic saturated, partially unsaturated or aryl    ring, a 5-6 membered monocyclic heteroaryl ring having 1-4    heteroatoms independently selected from nitrogen, oxygen, or sulfur,    a 3-7 membered saturated or partially unsaturated heterocyclic ring    having 1-3 heteroatoms independently selected from nitrogen, oxygen,    or sulfur, a 7-10 membered bicyclic saturated or partially    unsaturated heterocyclic ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, or an 8-10 membered    bicyclic heteroaryl ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur;-   R⁴ is an optionally substituted 5-membered monocyclic heteroaryl    ring having 1-2 nitrogen atoms; and-   each R′ is independently hydrogen or an optionally substituted group    selected from C₁₋₆ aliphatic, phenyl, a 3-7 membered saturated or    partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur; or:    -   two R′ groups on the same nitrogen atom are optionally taken        together with the nitrogen atom to form an optionally        substituted 3-8 membered, saturated, partially unsaturated, or        aryl ring having 1-4 heteroatoms independently selected from        nitrogen, oxygen, or sulfur.

In some embodiments, the present invention provides a compound offormula II:

wherein:

-   M is molybdenum or tungsten;-   R¹ is an optionally substituted group selected from C₁₋₂₀ aliphatic,    C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms independently selected    from nitrogen, oxygen, or sulfur, phenyl, a 3-7 membered saturated    or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur;-   R^(2′) and R^(3′) are taken together with their intervening metal    atoms to form an optionally substituted 3-8 membered saturated or    partially unsaturated ring having, in addition to the intervening    metal atom, 0-4 heteroatoms independently selected from nitrogen,    oxygen, or sulfur;-   m is 0-3;-   Ring B is an optionally substituted group selected from phenyl or a    5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms    independently selected from nitrogen, oxygen, or sulfur;-   each of p and q is independently 0-4;-   each of Ring C and Ring D is independently an optionally substituted    5-membered monocyclic heteroaryl ring having 1-4 nitrogen atoms;-   each of R^(x), R^(y) and R^(z) is independently halogen, —OR′,    —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)₂, —NR′SO₂R′,    —NR′SO₂N(R′)₂, —NR′OR′, or an optionally substituted group selected    from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, phenyl, a    3-7 membered saturated or partially unsaturated carbocyclic ring, an    8-10 membered bicyclic saturated, partially unsaturated or aryl    ring, a 5-6 membered monocyclic heteroaryl ring having 1-4    heteroatoms independently selected from nitrogen, oxygen, or sulfur,    a 3-7 membered saturated or partially unsaturated heterocyclic ring    having 1-3 heteroatoms independently selected from nitrogen, oxygen,    or sulfur, a 7-10 membered bicyclic saturated or partially    unsaturated heterocyclic ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, or an 8-10 membered    bicyclic heteroaryl ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur;-   R⁴ is an optionally substituted 5-membered monocyclic heteroaryl    ring having 1-2 nitrogen atoms; and-   each R′ is independently hydrogen or an optionally substituted group    selected from C₁₋₆ aliphatic, phenyl, a 3-7 membered saturated or    partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur; or:    -   two R′ groups on the same nitrogen atom are optionally taken        together with the nitrogen atom to form an optionally        substituted 3-8 membered, saturated, partially unsaturated, or        aryl ring having 1-4 heteroatoms independently selected from        nitrogen, oxygen, or sulfur.

In some embodiments, the present invention provides new methods forhighly efficient Z-selective metathesis reactions. In some embodiments,the present invention provides a method, comprising:

-   -   (a) providing a compound of formula I or II;    -   (b) reacting a first unsaturated bond and a second unsaturated        bond to produce a product comprising an unsaturated bond.

In some embodiments, a compound in a provided method is a compound offormula I. In some embodiments, a compound in a provided method is acompound of formula II. In some embodiments, a first unsaturated bond isan unsaturated carbon-carbon bond. In some embodiments, a secondunsaturated bond is an unsaturated carbon-carbon bond. In someembodiments, both the first and the second unsaturated bonds areunsaturated carbon-carbon bonds. In some embodiments, a productcomprising an unsaturated bond comprises an unsaturated carbon-carbonbond. In some embodiments, a product comprising an unsaturated bondcomprises an unsaturated carbon-carbon bond, wherein the unsaturatedcarbon-carbon bond comprises a carbon atom from the first unsaturatedbond and a carbon atom from the second unsaturated bond. In someembodiments, an unsaturated carbon-carbon bond is a double bond (C═C).In some embodiments, an unsaturated carbon-carbon bond is a triple bond(C═C).

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1. Thermal ellipsoid representation of the structure of 2b at the50% probability level. The solvent molecule and hydrogen atoms wereomitted for clarity.

FIG. 2. Thermal ellipsoid representation of the structure of 3b at the50% probability level. The solvent molecule and hydrogen atoms wereomitted for clarity.

FIG. 3. Thermal ellipsoid representation of the structure of 5 at the50% probability level. The minor component of the tungsten disorder andthe hydrogen atoms are omitted for clarity. Selected bond lengths (Å)and angles (°): W(1)-O(1) 1.986(2), W(1)-N(1) 2.031(1), W(1)-N(2)1.752(2), W(1)-C(1) 2.035(2), W(1)-C(3) 2.083(2), W····C2 2.370(2),C(1)-C(2) 1.603(3), C(2)-C(3) 1.590(3); O(1)-W(1)-N(1) 84.03(7),N(2)-W(1)-O(1) 166.13(7), N(2)-W(1)-C(3) 93.16(9), N(2)-W(1)-C(1)97.96(9), N(1)-W(1)-C(2) 165.65(8), W(1)-C(3)-C(2) 79.1(1),C(3)-C(2)-C(1) 117.5(2), C(2)-C(1)-W(1) 80.3(1), C(1)-W(1)-C(3)83.02(9), N(1)-W(1)-N(2) 91.27(8), N(1)-W(1)-C(3) 150.64(8).

FIG. 4. Thermal ellipsoid drawing (50%) of metallacyclobutane moiety in5 with bond lengths (Å) and angles (°).

FIG. 5. Selected distances and angles in five TBP structures (Avg) andone SP structure.

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS 1. General Description ofCertain Embodiments of the Invention

The present invention, among other things, provides new compounds thatcan be used as ligand or ligand precursor for the preparation ofcompounds that promotes highly efficient metathesis reactions thatselectively produce Z-olefins. In some embodiments, the presentinvention provides compounds that promote highly efficient Z-selectivemetathesis reactions. In some embodiments, the present inventionprovides new methods for metathesis reactions. In some embodiments, amethod comprising the use of a provided compound delivers up to 62%conversion and >95% Z-selectivity in the homocoupling of 1-octene in 10minutes. Among other things, the provided compounds and methods areuseful for the preparation of biologically active molecules andindustrially important chemicals.

In some embodiments, the present invention provides a compound offormula I:

wherein:

-   M is molybdenum or tungsten;-   R¹ is an optionally substituted group selected from C₁₋₂₀ aliphatic,    C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms independently selected    from nitrogen, oxygen, or sulfur, phenyl, a 3-7 membered saturated    or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur;-   each of R² and R³ is independently R′, —OR′, —SR′, —N(R′)₂,    —OC(O)R′, —SOR′, —SO₂R′, —SO₂N(R′)₂, —C(O)N(R′)₂, —NR′C(O)R′, or    —NR′SO₂R′;-   m is 0-3;-   Ring B is an optionally substituted group selected from phenyl or a    5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms    independently selected from nitrogen, oxygen, or sulfur;-   each of p and q is independently 0-4;-   each of Ring C and Ring D is independently an optionally substituted    5-membered monocyclic heteroaryl ring having 1-4 nitrogen atoms;-   each of R^(x), R^(y) and R^(z) is independently halogen, —OR′,    —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)₂, —NR′SO₂R′,    —NR′SO₂N(R′)₂, —NR′OR′, or an optionally substituted group selected    from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, phenyl, a    3-7 membered saturated or partially unsaturated carbocyclic ring, an    8-10 membered bicyclic saturated, partially unsaturated or aryl    ring, a 5-6 membered monocyclic heteroaryl ring having 1-4    heteroatoms independently selected from nitrogen, oxygen, or sulfur,    a 3-7 membered saturated or partially unsaturated heterocyclic ring    having 1-3 heteroatoms independently selected from nitrogen, oxygen,    or sulfur, a 7-10 membered bicyclic saturated or partially    unsaturated heterocyclic ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, or an 8-10 membered    bicyclic heteroaryl ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur;-   R⁴ is an optionally substituted 5-membered monocyclic heteroaryl    ring having 1-2 nitrogen atoms; and-   each R′ is independently hydrogen or an optionally substituted group    selected from C₁₋₆ aliphatic, phenyl, a 3-7 membered saturated or    partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur; or:    -   two R′ groups on the same nitrogen atom are optionally taken        together with the nitrogen atom to form an optionally        substituted 3-8 membered, saturated, partially unsaturated, or        aryl ring having 1-4 heteroatoms independently selected from        nitrogen, oxygen, or sulfur.

In some embodiments, the present invention provides a compound offormula II:

wherein:

-   M is molybdenum or tungsten;-   R¹ is an optionally substituted group selected from C₁₋₂₀ aliphatic,    C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms independently selected    from nitrogen, oxygen, or sulfur, phenyl, a 3-7 membered saturated    or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur;-   R^(2′) and R^(3′) are taken together with their intervening metal    atoms to form an optionally substituted 3-8 membered saturated or    partially unsaturated ring having, in addition to the intervening    metal atom, 0-4 heteroatoms independently selected from nitrogen,    oxygen, or sulfur;-   m is 0-3;-   Ring B is an optionally substituted group selected from phenyl or a    5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms    independently selected from nitrogen, oxygen, or sulfur;-   each of p and q is independently 0-4;-   each of Ring C and Ring D is independently an optionally substituted    5-membered monocyclic heteroaryl ring having 1-4 nitrogen atoms;-   each of R^(x), R^(y) and R^(z) is independently halogen, —OR′,    —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)₂, —NR′SO₂R′,    —NR′SO₂N(R′)₂, —NR′OR′, or an optionally substituted group selected    from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, phenyl, a    3-7 membered saturated or partially unsaturated carbocyclic ring, an    8-10 membered bicyclic saturated, partially unsaturated or aryl    ring, a 5-6 membered monocyclic heteroaryl ring having 1-4    heteroatoms independently selected from nitrogen, oxygen, or sulfur,    a 3-7 membered saturated or partially unsaturated heterocyclic ring    having 1-3 heteroatoms independently selected from nitrogen, oxygen,    or sulfur, a 7-10 membered bicyclic saturated or partially    unsaturated heterocyclic ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, or an 8-10 membered    bicyclic heteroaryl ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur;-   R⁴ is an optionally substituted 5-membered monocyclic heteroaryl    ring having 1-2 nitrogen atoms; and-   each R′ is independently hydrogen or an optionally substituted group    selected from C₁₋₆ aliphatic, phenyl, a 3-7 membered saturated or    partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur; or:    -   two R′ groups on the same nitrogen atom are optionally taken        together with the nitrogen atom to form an optionally        substituted 3-8 membered, saturated, partially unsaturated, or        aryl ring having 1-4 heteroatoms independently selected from        nitrogen, oxygen, or sulfur.

In some embodiments, the present invention provides a compound offormula III:

or its salt thereof,wherein:

-   m is 0-3;-   Ring B is an optionally substituted group selected from phenyl or a    5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms    independently selected from nitrogen, oxygen, or sulfur;-   each of p and q is independently 0-4;-   each of Ring C and Ring D is independently an optionally substituted    5-membered monocyclic heteroaryl ring having 1-4 nitrogen atoms;-   each of R^(x), R^(y) and R^(z) is independently halogen, —OR′,    —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)₂, —NR′SO₂R′,    —NR′SO₂N(R′)₂, —NR′OR′, or an optionally substituted group selected    from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, phenyl, a    3-7 membered saturated or partially unsaturated carbocyclic ring, an    8-10 membered bicyclic saturated, partially unsaturated or aryl    ring, a 5-6 membered monocyclic heteroaryl ring having 1-4    heteroatoms independently selected from nitrogen, oxygen, or sulfur,    a 3-7 membered saturated or partially unsaturated heterocyclic ring    having 1-3 heteroatoms independently selected from nitrogen, oxygen,    or sulfur, a 7-10 membered bicyclic saturated or partially    unsaturated heterocyclic ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, or an 8-10 membered    bicyclic heteroaryl ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur;-   each R′ is independently hydrogen or an optionally substituted group    selected from C₁₋₆ aliphatic, phenyl, a 3-7 membered saturated or    partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur; or:    -   two R′ groups on the same nitrogen atom are optionally taken        together with the nitrogen atom to form an optionally        substituted 3-8 membered, saturated, partially unsaturated, or        aryl ring having 1-4 heteroatoms independently selected from        nitrogen, oxygen, or sulfur.

In some embodiments, the present invention provides new methods forhighly efficient Z-selective metathesis reactions. In some embodiments,the present invention provides a method, comprising:

-   -   (a) providing a compound of formula I or II;    -   (b) reacting a first unsaturated bond and a second unsaturated        bond to produce a product comprising an unsaturated bond.

In some embodiments, the present invention provides a method,comprising:

-   -   (a) providing a compound of formula I or II;    -   (b) reacting a first carbon-carbon double bond with a second        carbon-carbon double to produce a product comprising a double        bond, wherein said double bond in the product comprises one        carbon atom from the first double bond and one carbon atom from        the second double bond.

2. Definitions

Compounds of the present invention include those described generallyherein, and are further illustrated by the classes, subclasses, andspecies disclosed herein. As used herein, the following definitionsshall apply unless otherwise indicated. For purposes of this invention,the chemical elements are identified in accordance with the PeriodicTable of the Elements, CAS version, Handbook of Chemistry and Physics,75^(th) Ed. Additionally, general principles of organic chemistry aredescribed in “Organic Chemistry”, Thomas Sorrell, University ScienceBooks, Sausalito: 1999, and “March's Advanced Organic Chemistry”, 5^(th)Ed., Ed.: Smith, M. B. and March, J., John Wiley & Sons, New York: 2001,the entire contents of which are hereby incorporated by reference.

The term “aliphatic” or “aliphatic group”, as used herein, means astraight-chain (i.e., unbranched) or branched, substituted orunsubstituted hydrocarbon chain that is completely saturated or thatcontains one or more units of unsaturation, or a monocyclic hydrocarbon,bicyclic hydrocarbon, or tricyclic hydrocarbon that is completelysaturated or that contains one or more units of unsaturation, but whichis not aromatic (also referred to herein as “carbocycle,”“cycloaliphatic” or “cycloalkyl”), that has a single point of attachmentto the rest of the molecule. Unless otherwise specified, aliphaticgroups contain 1-30 aliphatic carbon atoms. In some embodiments,aliphatic groups contain 1-20 aliphatic carbon atoms. In otherembodiments, aliphatic groups contain 1-10 aliphatic carbon atoms. Instill other embodiments, aliphatic groups contain 1-5 aliphatic carbonatoms, and in yet other embodiments, aliphatic groups contain 1, 2, 3,or 4 aliphatic carbon atoms. Suitable aliphatic groups include, but arenot limited to, linear or branched, substituted or unsubstituted alkyl,alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl,(cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

The term “cycloaliphatic,” as used herein, refers to saturated orpartially unsaturated cyclic aliphatic monocyclic, bicyclic, orpolycyclic ring systems, as described herein, having from 3 to 14members, wherein the aliphatic ring system is optionally substituted asdefined above and described herein. Cycloaliphatic groups include,without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl,cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl,cyclooctenyl, norbornyl, adamantyl, and cyclooctadienyl. In someembodiments, the cycloalkyl has 3-6 carbons. The terms “cycloaliphatic,”may also include aliphatic rings that are fused to one or more aromaticor nonaromatic rings, such as decahydronaphthyl or tetrahydronaphthyl,where the radical or point of attachment is on the aliphatic ring. Insome embodiments, a carbocyclic group is bicyclic. In some embodiments,a carbocyclic group is tricyclic. In some embodiments, a carbocyclicgroup is polycyclic. In some embodiments, “cycloaliphatic” (or“carbocycle” or “cycloalkyl”) refers to a monocyclic C₃-C₆ hydrocarbon,or a C₈-C₁₀ bicyclic hydrocarbon that is completely saturated or thatcontains one or more units of unsaturation, but which is not aromatic,that has a single point of attachment to the rest of the molecule, or aC₉-C₁₆ tricyclic hydrocarbon that is completely saturated or thatcontains one or more units of unsaturation, but which is not aromatic,that has a single point of attachment to the rest of the molecule.

As used herein, the term “alkyl” is given its ordinary meaning in theart and may include saturated aliphatic groups, including straight-chainalkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic)groups, alkyl substituted cycloalkyl groups, and cycloalkyl substitutedalkyl groups. In certain embodiments, a straight chain or branched chainalkyl has about 1-20 carbon atoms in its backbone (e.g., C₁-C₂₀ forstraight chain, C₂-C₂₀ for branched chain), and alternatively, about1-10. In some embodiments, a cycloalkyl ring has from about 3-10 carbonatoms in their ring structure where such rings are monocyclic orbicyclic, and alternatively about 5, 6 or 7 carbons in the ringstructure. In some embodiments, an alkyl group may be a lower alkylgroup, wherein a lower alkyl group comprises 1-4 carbon atoms (e.g.,C₁-C₄ for straight chain lower alkyls).

As used herein, the term “alkenyl” refers to an alkyl group, as definedherein, having one or more double bonds.

As used herein, the term “alkynyl” refers to an alkyl group, as definedherein, having one or more triple bonds.

The term “heteroalkyl” is given its ordinary meaning in the art andrefers to alkyl groups as described herein in which one or more carbonatoms is replaced with a heteroatom (e.g., oxygen, nitrogen, sulfur, andthe like). Examples of heteroalkyl groups include, but are not limitedto, alkoxy, poly(ethylene glycol)-, alkyl-substituted amino,tetrahydrofuranyl, piperidinyl, morpholinyl, etc.

The term “aryl” used alone or as part of a larger moiety as in“aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to monocyclic orbicyclic ring systems having a total of five to fourteen ring members,wherein at least one ring in the system is aromatic and wherein eachring in the system contains 3 to 7 ring members. The term “aryl” may beused interchangeably with the term “aryl ring.” In certain embodimentsof the present invention, “aryl” refers to an aromatic ring system whichincludes, but not limited to, phenyl, biphenyl, naphthyl, binaphthyl,anthracyl and the like, which may bear one or more substituents. Alsoincluded within the scope of the term “aryl,” as it is used herein, is agroup in which an aromatic ring is fused to one or more non-aromaticrings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, ortetrahydronaphthyl, and the like.

The terms “heteroaryl” and “heteroar-,” used alone or as part of alarger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer togroups having 5 to 10 ring atoms (i.e., monocyclic or bicyclic), in someembodiments 5, 6, 9, or 10 ring atoms. In some embodiments, such ringshave 6, 10, or 14 it electrons shared in a cyclic array; and having, inaddition to carbon atoms, from one to five heteroatoms. The term“heteroatom” refers to nitrogen, oxygen, or sulfur, and includes anyoxidized form of nitrogen or sulfur, and any quaternized form of a basicnitrogen. Heteroaryl groups include, without limitation, thienyl,furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl,oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl,thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl,purinyl, naphthyridinyl, and pteridinyl. In some embodiments, aheteroaryl is a heterobiaryl group, such as bipyridyl and the like. Theterms “heteroaryl” and “heteroar-”, as used herein, also include groupsin which a heteroaromatic ring is fused to one or more aryl,cycloaliphatic, or heterocyclyl rings, where the radical or point ofattachment is on the heteroaromatic ring. Nonlimiting examples includeindolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl,indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl,cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl,carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl,tetrahydroquinolinyl, tetrahydroisoquinolinyl, andpyrido[2,3-b]-1,4-oxazin-3(4H)-one. A heteroaryl group may be mono- orbicyclic. The term “heteroaryl” may be used interchangeably with theterms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any ofwhich terms include rings that are optionally substituted. The term“heteroaralkyl” refers to an alkyl group substituted by a heteroaryl,wherein the alkyl and heteroaryl portions independently are optionallysubstituted.

As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclicradical,” and “heterocyclic ring” are used interchangeably and refer toa stable 5- to 7-membered monocyclic or 7-10-membered bicyclicheterocyclic moiety that is either saturated or partially unsaturated,and having, in addition to carbon atoms, one or more, preferably one tofour, heteroatoms, as defined above. When used in reference to a ringatom of a heterocycle, the term “nitrogen” includes a substitutednitrogen. As an example, in a saturated or partially unsaturated ringhaving 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, thenitrogen may be N (as in 3,4-dihydro-2H-pyrrolyl), NH (as inpyrrolidinyl), or ⁺NR (as in N-substituted pyrrolidinyl).

A heterocyclic ring can be attached to its pendant group at anyheteroatom or carbon atom that results in a stable structure and any ofthe ring atoms can be optionally substituted. Examples of such saturatedor partially unsaturated heterocyclic radicals include, withoutlimitation, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl,piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl,decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl,diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. Theterms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclicgroup,” “heterocyclic moiety,” and “heterocyclic radical,” are usedinterchangeably herein, and also include groups in which a heterocyclylring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings,such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, ortetrahydroquinolinyl. A heterocyclyl group may be mono- or bicyclic. Theterm “heterocyclylalkyl” refers to an alkyl group substituted by aheterocyclyl, wherein the alkyl and heterocyclyl portions independentlyare optionally substituted.

As used herein, the term “partially unsaturated” refers to a ring moietythat includes at least one double or triple bond. The term “partiallyunsaturated” is intended to encompass rings having multiple sites ofunsaturation, but is not intended to include aryl or heteroarylmoieties, as herein defined.

The term “heteroatom” means one or more of oxygen, sulfur, nitrogen,phosphorus, or silicon (including, any oxidized form of nitrogen,sulfur, phosphorus, or silicon; the quaternized form of any basicnitrogen or; a substitutable nitrogen of a heterocyclic ring, forexample N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) orNR⁺ (as in N-substituted pyrrolidinyl)).

The term “unsaturated,” as used herein, means that a moiety has one ormore units of unsaturation.

The term “halogen” means F, Cl, Br, or I.

As described herein, compounds of the invention may contain “optionallysubstituted” moieties. In general, the term “substituted,” whetherpreceded by the term “optionally” or not, means that one or morehydrogens of the designated moiety are replaced with a suitablesubstituent. Unless otherwise indicated, an “optionally substituted”group may have a suitable substituent at each substitutable position ofthe group, and when more than one position in any given structure may besubstituted with more than one substituent selected from a specifiedgroup, the substituent may be either the same or different at everyposition. Combinations of substituents envisioned by this invention arepreferably those that result in the formation of stable or chemicallyfeasible compounds. The term “stable,” as used herein, refers tocompounds that are not substantially altered when subjected toconditions to allow for their production, detection, and, in certainembodiments, their recovery, purification, and use for one or more ofthe purposes disclosed herein.

Suitable monovalent substituents on a substitutable carbon atom of an“optionally substituted” group are independently halogen;—(CH₂)₀₋₄R^(∘); —(CH₂)₀₋₄OR^(∘); —O(CH₂)₀₋₄R^(∘), —O—(CH₂)₀₋₄C(O)OR^(∘);—(CH₂)₀₋₄CH(OR^(∘))₂; —(CH₂)₀₋₄Ph, which may be substituted with R^(∘);—(CH₂)₀₋₄O(CH₂)₀₋₁Ph which may be substituted with R^(∘); —CH═CHPh,which may be substituted with R^(∘); —(CH₂)₀₋₄O(CH₂)₀₋₁-pyridyl whichmay be substituted with R^(∘); —NO₂; —CN; —N₃; —(CH₂)₀₋₄N(R^(∘))₂;—(CH₂)₀₋₄N(R^(∘))C(O)R^(∘); —N(R^(∘))C(S)R^(∘); —(CH₂)₀₋₄N(R)C(O)NR₂;—N(R^(∘))C(S)NR^(∘) ₂; —(CH₂)₀₋₄N(R^(∘))C(O)OR^(∘);—N(R^(∘))N(R^(∘))C(O)R^(∘); —N(R^(∘))N(R^(∘))C(O)NR^(∘) ₂;—N(R^(∘))N(R^(∘))C(O)OR^(∘); —(CH₂)₀₋₄C(O)R^(∘); —C(S)R^(∘);—(CH₂)₀₋₄C(O)OR^(∘); —(CH₂)₀₋₄C(O)SR^(∘); —(CH₂)₀₋₄C(O)OSiR^(∘) ₃;—(CH₂)₀₋₄OC(O)R^(∘); —OC(O)(CH₂)₀₋₄SR—, SC(S)SR^(∘);—(CH₂)₀₋₄SC(O)R^(∘); —(CH₂)₀₋₄C(O)NR^(∘) ₂; —C(S)NR^(∘) ₂; —C(S)SR^(∘);—SC(S)SR^(∘), —(CH₂)₀₋₄OC(O)NR^(∘) ₂; —C(O)N(OR^(∘))R^(∘);—C(O)C(O)R^(∘); —C(O)CH₂C(O)R^(∘); —C(NOR^(∘))R^(∘); —(CH₂)₀₋₄SSR^(∘);—(CH₂)₀₋₄S(O)₂R^(∘); —(CH₂)₀₋₄S(O)₂OR^(∘); —(CH₂)₀₋₄OS(O)₂R^(∘);—S(O)₂NR^(∘) ₂; —(CH₂)₀₋₄S(O)R^(∘); —N(R^(∘))S(O)₂NR^(∘) ₂;—N(R^(∘))S(O)₂R^(∘); —N(OR^(∘))R^(∘); —C(NH)NR^(∘) ₂; —P(O)₂R^(∘);—P(O)R^(∘) ₂; —OP(O)R^(∘) ₂; —OP(O)(OR^(∘))₂; —SiR^(∘) ₃; —OSiR^(∘) ₃;—(C₁₋₄ straight or branched alkylene)O—N(R^(∘))₂; or —(C₁₋₄ straight orbranched alkylene)C(O)O—N(R^(∘))₂, wherein each R^(∘) may be substitutedas defined below and is independently hydrogen, C₁₋₆ aliphatic, —CH₂Ph,—O(CH₂)₀₋₁Ph, —CH₂-(5-6 membered heteroaryl ring), or a 5-6-memberedsaturated, partially unsaturated, or aryl ring having 0-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, or,notwithstanding the definition above, two independent occurrences ofR^(∘), taken together with their intervening atom(s), form a3-12-membered saturated, partially unsaturated, or aryl mono- orbicyclic ring having 0-4 heteroatoms independently selected fromnitrogen, oxygen, or sulfur, which may be substituted as defined below.

Suitable monovalent substituents on R^(∘) (or the ring formed by takingtwo independent occurrences of R^(∘) together with their interveningatoms), are independently halogen, —(CH₂)₀₋₂R^(•), -(haloR^(•)),—(CH₂)₀₋₂OH, —(CH₂)₀₋₂OR^(•), —(CH₂)₀₋₂CH(OR^(•))₂; —O(haloR^(•)), —CN,—N₃, —(CH₂)₀₋₂C(O)R^(•), —(CH₂)₀₋₂C(O)OH, —(CH₂)₀₋₂C(O)OR^(•),—(CH₂)₀₋₂SR^(•), —(CH₂)₀₋₂SH, —(CH₂)₀₋₂NH₂, —(CH₂)₀₋₂NHR^(•),—(CH₂)₀₋₂NR^(•) ₂, —NO₂, —SiR^(•) ₃, —OSiR^(•) ₃, —C(O)SR^(•), —(C₁₋₄straight or branched alkylene)C(O)OR^(•), or —SSR^(•) wherein each R^(•)is unsubstituted or where preceded by “halo” is substituted only withone or more halogens, and is independently selected from C₁₋₄ aliphatic,—CH₂Ph, —O(CH₂)₀₋₁Ph, or a 5-6-membered saturated, partiallyunsaturated, or aryl ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur. Suitable divalent substituents on asaturated carbon atom of R^(∘) include ═O and ═S.

Suitable divalent substituents on a saturated carbon atom of an“optionally substituted” group include the following: ═O, ═S, ═NNR*₂,═NNHC(O)R*, ═NNHC(O)OR*, ═NNHS(O)₂R*, ═NR*, ═NOR*, —O(C(R*₂))₂₋₃O—, or—S(C(R*₂))₂₋₃S—, wherein each independent occurrence of R* is selectedfrom hydrogen, C₁₋₆ aliphatic which may be substituted as defined below,or an unsubstituted 5-6-membered saturated, partially unsaturated, oraryl ring having 0-4 heteroatoms independently selected from nitrogen,oxygen, or sulfur. Suitable divalent substituents that are bound tovicinal substitutable carbons of an “optionally substituted” groupinclude: —O(CR*₂)₂₋₃O—, wherein each independent occurrence of R* isselected from hydrogen, C₁₋₆ aliphatic which may be substituted asdefined below, or an unsubstituted 5-6-membered saturated, partiallyunsaturated, or aryl ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur.

Suitable substituents on the aliphatic group of R* include halogen,—R^(•), -(haloR^(•)), —OH, —OR^(•), —O(haloR^(•)), —CN, —C(O)OH,—C(O)OR^(•), —NH₂, —NHR^(•), —NR^(•) ₂, or —NO₂, wherein each R^(•) isunsubstituted or where preceded by “halo” is substituted only with oneor more halogens, and is independently C₁₋₄ aliphatic, —CH₂Ph,—O(CH₂)₀₋₁Ph, or a 5-6-membered saturated, partially unsaturated, oraryl ring having 0-4 heteroatoms independently selected from nitrogen,oxygen, or sulfur.

Suitable substituents on a substitutable nitrogen of an “optionallysubstituted” group include —R^(†), —NR^(†) ₂, —C(O)R^(†), —C(O)OR^(†),—C(O)C(O)R^(†), —C(O)CH₂C(O)R^(†), —S(O)₂R^(†), —S(O)₂NR^(†) ₂,—C(S)NR^(†) ₂, —C(NH)NR^(†) ₂, or —N(R^(†))S(O)₂R^(†); wherein eachR^(†) is independently hydrogen, C₁₋₆ aliphatic which may be substitutedas defined below, unsubstituted —OPh, or an unsubstituted 5-6-memberedsaturated, partially unsaturated, or aryl ring having 0-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, or,notwithstanding the definition above, two independent occurrences ofR^(†), taken together with their intervening atom(s) form anunsubstituted 3-12-membered saturated, partially unsaturated, or arylmono- or bicyclic ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur.

Suitable substituents on the aliphatic group of R^(†) are independentlyhalogen, —R^(•), -(haloR^(•)), —OH, —OR^(•), —O(haloR^(•)), —CN,—C(O)OH, —C(O)OR^(•), —NH₂, —NHR^(•), —NR^(•) ₂, or —NO₂, wherein eachR^(•) is unsubstituted or where preceded by “halo” is substituted onlywith one or more halogens, and is independently C₁₋₄ aliphatic, —CH₂Ph,—O(CH₂)₀₋₁Ph, or a 5-6-membered saturated, partially unsaturated, oraryl ring having 0-4 heteroatoms independently selected from nitrogen,oxygen, or sulfur.

As used herein, the term “stereogenic metal atom” is given its ordinarymeaning, and refers to a metal atom coordinated by at least two ligands(e.g., at least four ligands), wherein the ligands are arranged aboutthe metal atom such that the overall structure (e.g., metal complex)lacks a plane of symmetry with respect to the metal atom. In some cases,the stereogenic metal atom may be coordinated by at least three ligands,at least four ligands, at least five ligands, at least six ligands, ormore. In certain embodiments, the stereogenic metal atom may becoordinated by four ligands. Metal complexes comprising a stereogenicmetal center may provide sufficient space specificity at a reaction siteof the metal complex, such that a molecular substrate having a plane ofsymmetry may be reacted at the reaction site to form a product that isfree of a plane of symmetry. That is, the stereogenic metal center ofthe metal complex may impart sufficient shape specificity to inducestereogenicity effectively, producing a chiral product. Such metalcomplexes may exhibit improved catalytic activity and stereoselectivity,relative to previous systems, and may reduce undesired side reactions(e.g., dimerization or oligomerization of the metal complex).

The term “chiral” is given its ordinary meaning in the art and refers toa molecule that is not superimposable with its mirror image, wherein theresulting nonsuperimposable mirror images are known as “enantiomers” andare labeled as either an (R) enantiomer or an (S) enantiomer. Typically,chiral molecules lack a plane of symmetry.

The term “achiral” is given its ordinary meaning in the art and refersto a molecule that is superimposable with its mirror image. Typically,achiral molecules possess a plane of symmetry.

As used herein, a ligand may be either monodentate or polydentate. Insome embodiments, a ligand is monodentate. In some embodiments, a ligandis bidentate. In some embodiments, a ligand is tridentate. In someembodiments, two or more monodentate ligands are taken together to forma polydentate ligand. A ligand may have hapticity of more than one. Insome cases, a ligand has a hapticity of 1 to 10. In some embodiments, aligand has a hapticity of 1. In some embodiments, a ligand has ahapticity of 2. In some embodiments, a ligand has a hapticity of 3. Insome embodiments, a ligand has a hapticity of 4. In some embodiments, aligand has a hapticity of 5. In some embodiments, a ligand has ahapticity of 6. For a ligand having hapticity greater than one, assometimes done in the art, a single bond may be drawn between the ligandand the metal. In some cases, a ligand is alkylidene. In some cases, aligand is a nitrogen-containing ligand. In some cases, a ligand is anoxygen-containing ligand. In some cases, a ligand is aphosphorus-containing ligand. In some embodiments, a ligand comprises anunsaturated bond, and the unsaturated bond is coordinated to a metal. Insome embodiments, a ligand comprises a carbon-carbon double bond, andthe double bond is coordinated to a metal. In some embodiments, a ligandis an olefin. When an olefin double bond is coordinated to a metal, thechemical bonding between the olefin and the metal can either be depictedas a 3-membered ring wherein the ring members comprises the metal andboth carbon atoms of the double bond, or as a single bond between themetal and the double bond.

As used herein, a “nitrogen-containing ligand” may be any speciescomprising a nitrogen atom. In some cases, the nitrogen atom may bind tothe metal atom. In some cases, the nitrogen-containing ligand may bindthe metal center via a different atom. In some cases, the nitrogen atommay be a ring atom of a heteroaryl or heteroalkyl group. In some cases,the nitrogen atom may be a substituted amine group. It should beunderstood that, in catalyst precursors described herein, thenitrogen-containing ligand may have sufficiently ionic character tocoordinate a metal center, such as a Mo or W metal center. Examples ofnitrogen-containing ligands include, but are not limited to, pyrrolyl,pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, imidazolyl, triazolyl,tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, indolyl,indazolyl, carbazolyl, morpholinyl, piperidinyl, oxazinyl, substitutedderivatives thereof, and the like. For example, the nitrogen-containingligand may be pyrrolide or 2,5-dimethylpyrrolide. Thenitrogen-containing ligand may be selected to interact with anoxygen-containing ligand such that the oxygen-containing ligand canreadily replace the nitrogen-containing ligand in a precatalyst togenerate a catalyst. In cases where the catalyst composition may begenerated in situ in order to carry out a chemical reaction, the first,nitrogen-containing ligand may be selected such that, upon replacementby an oxygen-containing ligand, the nitrogen-containing ligands orprotonated versions thereof do not interfere with the chemical reaction.In some embodiments, the nitrogen-containing ligand may be chiral andthe precatalyst may be provided as a racemic mixture or a purifiedstereoisomer.

In some embodiments, a nitrogen-containing ligand may also describe aligand precursor comprising at least one hydrogen atom directly bondedto a nitrogen atom, wherein deprotonation of the at least one hydrogenatom results in a negatively charged nitrogen atom, which may coordinateto a metal atom. Exemplary such precursors include but are not limitedto amines, amides, and pyrrole and its derivatives thereof. Anitrogen-containing ligand may be a heteroaryl or heteroalkyl groupcomprising at least one nitrogen ring atom. In some cases, the nitrogenatom may be positioned on a substituent of an alkyl, heteroalkyl, aryl,or heteroaryl group. For example, a nitrogen-containing ligand may be anamine- or amide-substituted aryl group, wherein the amine or amide groupis deprotonated upon coordination to the metal center.

As used herein, the term “oxygen-containing ligand” may be used to referto ligands comprising at least one oxygen atom. In some cases, theoxygen atom binds to the metal atom thereby forming an ether-linkage. Inother cases, the oxygen-containing ligand may bind the metal center viaa different atom. The term “oxygen-containing ligand” may also describeligand precursors comprising at least one hydroxyl group (e.g., ahydroxyl-containing ligand), wherein deprotonation of the hydroxyl groupresults in a negatively charged oxygen atom, which may coordinate to ametal atom. The oxygen-containing ligand may be a heteroaryl orheteroalkyl group comprising at least one oxygen ring atom. In somecases, the oxygen atom may be positioned on a substituent of an alkyl,heteroalkyl, aryl, or heteroaryl group. For example, theoxygen-containing ligand may be a hydroxy-substituted aryl group,wherein the hydroxyl group is deprotonated upon coordination to themetal center.

In some embodiments, an oxygen-containing ligand may also describe aligand precursor comprising at least one hydroxyl group (e.g., ahydroxyl-containing ligand), wherein deprotonation of the hydroxyl groupresults in a negatively charged oxygen atom, which may coordinate to ametal atom. An oxygen-containing ligand may be a heteroaryl orheteroalkyl group comprising at least one oxygen ring atom. In somecases, the oxygen atom may be positioned on a substituent of an alkyl,heteroalkyl, aryl, or heteroaryl group. For example, anoxygen-containing ligand may be a hydroxy-substituted aryl group,wherein the hydroxyl group is deprotonated upon coordination to themetal center.

As used herein, the term “phosphorus-containing ligand” may be used torefer to ligands comprising at least one phosphorus atom. In some cases,the phosphorus atom binds to the metal. In other cases, thephosphorus-containing ligand may bind to the metal center via adifferent atom (i.e., an atom other than the phosphorous). Thephosphorus-containing ligand may have phosphorus atom of variousoxidation states. In some cases the phosphorus-containing ligand isphosphine. In some cases the phosphorus-containing ligand is phosphite.In some cases the phosphorus-containing ligand is phosphate. Thephosphorus-containing ligand may be either monodentate or polydentate.In some cases, two or more phosphorus atoms bind to the metal. In somecases, one or more phosphorus atoms together with one or morenon-phosphorus atoms bind to the metal.

As defined herein, a “metal complex” is any complex used to form aprovided precursor complex or any complex generated from a providedprecursor complex (e.g., for use as a catalyst in a reaction such as ametathesis reaction). In some embodiments, a metal complex is a compoundhaving the structure of formula I described herein. In some embodiments,a metal complex is a compound having the structure of formula IIdescribed herein.

The phrase “protecting group,” as used herein, refers to temporarysubstituents which protect a potentially reactive functional group fromundesired chemical transformations. Examples of such protecting groupsinclude esters of carboxylic acids, silyl ethers of alcohols, andacetals and ketals of aldehydes and ketones, respectively. A “Siprotecting group” is a protecting group comprising a Si atom, such asSi-trialkyl (e.g., trimethylsilyl, tributylsilyl, t-butyldimethylsilyl),Si-triaryl, Si-alkyl-diphenyl (e.g., t-butyldiphenylsilyl), orSi-aryl-dialkyl (e.g., Si-phenyldialkyl). Generally, a Si protectinggroup is attached to an oxygen atom. The field of protecting groupchemistry has been reviewed (Greene, T. W.; Wuts, P. G. M. ProtectiveGroups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). Suchprotecting groups (and associated protected moieties) are described indetail below.

Protected hydroxyl groups are well known in the art and include thosedescribed in detail in Protecting Groups in Organic Synthesis, T. W.Greene and P. G. M. Wuts, 3^(rd) edition, John Wiley & Sons, 1999, theentirety of which is incorporated herein by reference. Examples ofsuitably protected hydroxyl groups further include, but are not limitedto, esters, carbonates, sulfonates, allyl ethers, ethers, silyl ethers,alkyl ethers, arylalkyl ethers, and alkoxyalkyl ethers. Examples ofsuitable esters include formates, acetates, proprionates, pentanoates,crotonates, and benzoates. Specific examples of suitable esters includeformate, benzoyl formate, chloroacetate, trifluoroacetate,methoxyacetate, triphenylmethoxyacetate, p-chlorophenoxyacetate,3-phenylpropionate, 4-oxopentanoate, 4,4-(ethylenedithio)pentanoate,pivaloate (trimethylacetate), crotonate, 4-methoxy-crotonate, benzoate,p-benzylbenzoate, 2,4,6-trimethylbenzoate. Examples of suitablecarbonates include 9-fluorenylmethyl, ethyl, 2,2,2-trichloroethyl,2-(trimethylsilyl)ethyl, 2-(phenylsulfonyl)ethyl, vinyl, allyl, andp-nitrobenzyl carbonate. Examples of suitable silyl ethers includetrimethylsilyl, triethylsilyl, t-butyldimethylsilyl,t-butyldiphenylsilyl, triisopropylsilyl ether, and other trialkylsilylethers. Examples of suitable alkyl ethers include methyl, benzyl,p-methoxybenzyl, 3,4-dimethoxybenzyl, trityl, t-butyl, and allyl ether,or derivatives thereof. Alkoxyalkyl ethers include acetals such asmethoxymethyl, methylthiomethyl, (2-methoxyethoxy)methyl,benzyloxymethyl, beta-(trimethylsilyl)ethoxymethyl, andtetrahydropyran-2-yl ether. Examples of suitable arylalkyl ethersinclude benzyl, p-methoxybenzyl (MPM), 3,4-dimethoxybenzyl,O-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl,p-cyanobenzyl, 2- and 4-picolyl ethers.

Protected amines are well known in the art and include those describedin detail in Greene (1999). Suitable mono-protected amines furtherinclude, but are not limited to, aralkylamines, carbamates, allylamines, amides, and the like. Examples of suitable mono-protected aminomoieties include t-butyloxycarbonylamino (—NHBOC),ethyloxycarbonylamino, methyloxycarbonylamino,trichloroethyloxycarbonylamino, allyloxycarbonylamino (—NHAlloc),benzyloxocarbonylamino (—NHCBZ), allylamino, benzylamino (—NHBn),fluorenylmethylcarbonyl (—NHFmoc), formamido, acetamido,chloroacetamido, dichloroacetamido, trichloroacetamido, phenylacetamido,trifluoroacetamido, benzamido, t-butyldiphenylsilyl, and the like.Suitable di-protected amines include amines that are substituted withtwo substituents independently selected from those described above asmono-protected amines, and further include cyclic imides, such asphthalimide, maleimide, succinimide, and the like. Suitable di-protectedamines also include pyrroles and the like,2,2,5,5-tetramethyl-[1,2,5]azadisilolidine and the like, and azide.

Protected aldehydes are well known in the art and include thosedescribed in detail in Greene (1999). Suitable protected aldehydesfurther include, but are not limited to, acyclic acetals, cyclicacetals, hydrazones, imines, and the like. Examples of such groupsinclude dimethyl acetal, diethyl acetal, diisopropyl acetal, dibenzylacetal, bis(2-nitrobenzyl)acetal, 1,3-dioxanes, 1,3-dioxolanes,semicarbazones, and derivatives thereof.

Protected carboxylic acids are well known in the art and include thosedescribed in detail in Greene (1999). Suitable protected carboxylicacids further include, but are not limited to, optionally substitutedC₁₋₆ aliphatic esters, optionally substituted aryl esters, silyl esters,activated esters, amides, hydrazides, and the like. Examples of suchester groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl,benzyl, and phenyl ester, wherein each group is optionally substituted.Additional suitable protected carboxylic acids include oxazolines andortho esters.

Protected thiols are well known in the art and include those describedin detail in Greene (1999). Suitable protected thiols further include,but are not limited to, disulfides, thioethers, silyl thioethers,thioesters, thiocarbonates, and thiocarbamates, and the like. Examplesof such groups include, but are not limited to, alkyl thioethers, benzyland substituted benzyl thioethers, triphenylmethyl thioethers, andtrichloroethoxycarbonyl thioester, to name but a few.

Unless otherwise stated, structures depicted herein are also meant toinclude all isomeric (e.g., enantiomeric, diastereomeric, and geometric(or conformational)) forms of the structure; for example, the R and Sconfigurations for each asymmetric center, (Z) and (E) double bondisomers, and (Z) and (E) conformational isomers. Therefore, singlestereochemical isomers as well as enantiomeric, diastereomeric, andgeometric (or conformational) mixtures of the present compounds arewithin the scope of the invention.

Unless otherwise stated, all tautomeric forms of the compounds of theinvention are within the scope of the invention.

Additionally, unless otherwise stated, structures depicted herein arealso meant to include compounds that differ only in the presence of oneor more isotopically enriched atoms. For example, compounds having thepresent structures except for the replacement of hydrogen by deuteriumor tritium, or the replacement of a carbon by a ¹¹C- or ¹³C- or¹⁴C-enriched carbon are within the scope of this invention. Suchcompounds are useful, for example, as analytical tools or probes inbiological assays.

As used herein and in the claims, the singular forms “a”, “an”, and“the” include the plural reference unless the context clearly indicatesotherwise. Thus, for example, a reference to “a compound” includes aplurality of such compounds.

3. Description of Certain Embodiments of the Invention

The present invention, among other things, encompasses the recognitionthat new catalysts and methods for highly efficient Z-selectivemetathesis reactions are needed. In some embodiments, the presentinvention provides new compounds as sterically demanding ligands orligand precursors suitable for preparation of compounds that promoteZ-selective metathesis reactions. In some embodiments, a new stericallydemanding ligand or ligand precursor is an aryloxide ligand. In someembodiments, the present invention provides new compounds that promotemetathesis reactions. In some embodiments, a provided compound comprisesa new sterically demanding ligand. In some embodiments, a providedcompound comprises a new sterically demanding aryloxide ligand. In someembodiments, a provided compound is a MAP compound comprising a newsterically demanding aryloxide ligand. In some embodiments, the presentinvention provides new methods for metathesis reactions. In someembodiments, a provided method produces Z-alkenes with unprecedentedefficiency and/or selectivity.

As used herein, the term “metathesis reaction” is given its ordinarymeaning in the art and refers to a chemical reaction in which tworeacting species exchange partners. In some embodiments, a metathesisreaction is performed in the presence of a transition-metal catalyst. Insome cases, a byproduct of a metathesis reaction may be ethylene. Ametathesis reaction may involve reaction between species comprising, forexample, olefins and/or alkynes. Examples of different kinds ofmetathesis reactions include cross metathesis, ring-closing metathesis,ring-opening metathesis, acyclic diene metathesis, alkyne metathesis,enyne metathesis, olefin metathesis and the like. A metathesis reactionmay occur between two substrates which are not joined by a bond (e.g.,intermolecular metathesis reaction) or between two portions of a singlesubstrate (e.g., intramolecular metathesis reaction). In someembodiments, two substrates of a metathesis reaction are identical. Insome embodiments, a provided compound of the present invention is usefulin the formation of a metathesis product with high efficiency and highZ-selectivity.

As defined above, M is molybdenum or tungsten. In some embodiments, M ismolybdenum. In other embodiments, M is tungsten.

As defined generally above, R¹ is an optionally substituted groupselected from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3heteroatoms independently selected from nitrogen, oxygen, or sulfur,phenyl, a 3-7 membered saturated or partially unsaturated carbocyclicring, an 8-10 membered bicyclic saturated, partially unsaturated or arylring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 3-7 memberedsaturated or partially unsaturated heterocyclic ring having 1-3heteroatoms independently selected from nitrogen, oxygen, or sulfur, a7-10 membered bicyclic saturated or partially unsaturated heterocyclicring having 1-5 heteroatoms independently selected from nitrogen,oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R¹ is optionally substituted C₁₋₂₀ aliphatic. Insome embodiments, R¹ is optionally substituted C₁₋₂₀ cycloaliphatic. Insome embodiments, R¹ is optionally substituted C₁₋₁₂ aliphatic. In someembodiments, R¹ is optionally substituted C₁₋₁₂ cycloaliphatic. In someembodiments, R¹ is optionally substituted C₁₋₁₂ cycloalkyl. In someembodiments, R¹ is optionally substituted adamantyl. In someembodiments, R¹ is adamantyl. In some embodiments, R¹ is optionallysubstituted C₁₋₆ aliphatic. In some embodiments, R¹ is optionallysubstituted C₁₋₆ alkyl. In some embodiments, R¹ is optionallysubstituted hexyl, pentyl, butyl, propyl, ethyl or methyl. In someembodiments, R¹ is optionally substituted hexyl. In some embodiments, R¹is optionally substituted pentyl. In some embodiments, R¹ is optionallysubstituted butyl. In some embodiments, R¹ is optionally substitutedpropyl. In some embodiments, R¹ is optionally substituted ethyl. In someembodiments, R¹ is optionally substituted methyl. In some embodiments,R¹ is hexyl. In some embodiments, R¹ is pentyl. In some embodiments, R¹is butyl. In some embodiments, R¹ is propyl. In some embodiments, R¹ isethyl. In some embodiments, R¹ is methyl. In some embodiments, R¹ isisopropyl.

In certain embodiments, R¹ is optionally substituted phenyl. In someembodiments, R¹ is substituted phenyl. In some embodiments, R¹ is mono-,di-, tri-, tetra- or penta-substituted phenyl. In some embodiments, R¹is mono-substituted phenyl. In certain embodiments, R¹ is2,6-disubstituted phenyl. In some embodiments, R¹ is tri-substitutedphenyl. In some embodiments, R¹ is tetra-substituted phenyl. In someembodiments, R¹ is penta-substituted phenyl. In some embodiments, asubstituent is a halogen. In some embodiments, a substituent is —F, andR¹ is phenyl substituted with one or more —F. In some embodiments, R¹ ispentafluorophenyl. In some embodiments, a substituent is optionallysubstituted C₁₋₄ aliphatic. In some embodiments, R¹ is phenyldisubstituted with halogen or C₁₋₄ aliphatic. Such R¹ groups include butare not limited to 2,6-dichlorophenyl, 2,6-dibromophenyl,2,6-dimethylphenyl, 2,6-di-tert-butylphenyl, and 2,6-diisopropylphenyl.

In some embodiments, R¹ is selected from:

As defined generally above, each of R² and R³ is independently R′, —OR′,—SR′, —N(R′)₂, —OC(O)R′, —SOR′, —SO₂R′, —SO₂N(R′)₂, —C(O)N(R′)₂,—NR′C(O)R′, or —NR′SO₂R′, wherein each R′ is independently as definedabove and described herein.

In some embodiments, both of R² and R³ are hydrogen. In someembodiments, one of R² and R³ is hydrogen and the other is an optionallysubstituted group selected from C₁₋₆ aliphatic, phenyl, a 3-7 memberedsaturated or partially unsaturated carbocyclic ring, an 8-10 memberedbicyclic saturated, partially unsaturated or aryl ring, a 5-6 memberedmonocyclic heteroaryl ring having 1-4 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclicsaturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, —OR′, —SR′,—N(R′)₂, —OC(O)R′, —SOR′, —SO₂R′, —SO₂N(R′)₂, —C(O)N(R′)₂, —NR′C(O)R′,or —NR′SO₂R′. In some embodiments, one of R² and R³ is hydrogen and theother is an optionally substituted group selected from C₁₋₆ aliphatic, a3-7 membered saturated or partially unsaturated carbocyclic ring, an8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a5-6 membered monocyclic heteroaryl ring having 1-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 4-7 memberedsaturated or partially unsaturated heterocyclic ring having 1-3heteroatoms independently selected from nitrogen, oxygen, or sulfur, a7-10 membered bicyclic saturated or partially unsaturated heterocyclicring having 1-5 heteroatoms independently selected from nitrogen,oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

In certain embodiments, R² or R³ is optionally substituted C₁₋₆aliphatic. In some embodiments, R² or R³ is optionally substituted C₁₋₆alkyl. In certain embodiments, R² or R³ is C₁₋₆ alkyl substituted withphenyl and one or two additional substituents. In certain embodiments,R² or R³ is a lower alkyl group optionally substituted with one or twomethyl groups and phenyl. In certain embodiments, R² or R³ is —C(Me)₂Ph.In certain embodiments, R² or R³ is —C(Me)₃.

In some embodiments, each of R² and R³ is independently R′, wherein R′is as defined above and described herein. In some embodiments, each ofR² and R³ is independently R′, wherein at least one of R² and R³ is nothydrogen.

In certain embodiments, R² is hydrogen and R³ is R′, —OR′, —SR′,—N(R′)₂, —OC(O)R′, —SOR′, —SO₂R′, —SO₂N(R′)₂, —C(O)N(R′)₂, —NR′C(O)R′,or —NR′SO₂R′, wherein each R′ is independently as defined above anddescribed herein. In certain embodiments, R² is hydrogen and R³ is R′,wherein R′ is as defined above and described herein. In certainembodiments, R² is hydrogen and R³ is optionally substituted C₁₋₂₀aliphatic. In some embodiments, R² is hydrogen and R³ is optionallysubstituted C₁₋₂₀ alkyl. In certain embodiments, R² is hydrogen and R³is C₁₋₆ alkyl substituted with phenyl and one or two additionalsubstituents. In certain embodiments, R² is hydrogen and R³ is a loweralkyl group optionally substituted with one or two methyl groups andphenyl. In certain embodiments, R² is hydrogen and R³ is —C(Me)₂Ph. Incertain embodiments, R² is hydrogen and R³ is —C(Me)₃.

As generally defined above, m is 0-3. In some embodiments, m is 0. Insome embodiments, m is 1-3. In some embodiments, m is 1. In someembodiments, m is 2. In some embodiments, m is 3. In some embodiments, mis 0-2.

As generally defined above, Ring B is an optionally substituted groupselected from phenyl or a 5-6 membered monocyclic heteroaryl ring having1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.In some embodiments, Ring B is of the following structure:

wherein R^(x) and m are as defined above and described herein. In someembodiments, Ring B is optionally substituted phenyl. In someembodiments, m=0. In some embodiments, Ring B is

In some embodiments, Ring B is an optionally substituted 5-6 memberedmonocyclic heteroaryl ring having 1-4 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur. In some embodiments, Ring B is anoptionally substituted 5-membered monocyclic heteroaryl ring having 1-4heteroatoms independently selected from nitrogen, oxygen, or sulfur, andm is 0-2. In some embodiments, Ring B is an optionally substituted6-membered monocyclic heteroaryl ring having 1-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, and m is 0-3.

In some embodiments, Ring B is a 5-6 membered monocyclic heteroaryl ringhaving 1-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, Ring B is a 5-6 membered monocyclicheteroaryl ring having 1-2 heteroatoms independently selected fromnitrogen, oxygen, or sulfur.

In some embodiments, Ring B is a 5-membered monocyclic heteroaryl ringhaving 1-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, Ring B is a 5-membered monocyclicheteroaryl ring having 1-2 heteroatoms independently selected fromnitrogen, oxygen, or sulfur.

In some embodiments, Ring B is a 6-membered monocyclic heteroaryl ringhaving 1-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, Ring B is a 6-membered monocyclicheteroaryl ring having 1-2 heteroatoms independently selected fromnitrogen, oxygen, or sulfur.

Exemplary optionally substituted Ring B heteroaryl groups includethienylene, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl,tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl,thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, and thelike.

As generally defined above, each of p and q is independently 0-4. Insome embodiments, p is 0. In some embodiments, p is 1-4. In someembodiments, p is 1. In some embodiments, p is 2. In some embodiments, pis 3. In some embodiments, p is 4.

In some embodiments, q is 0. In some embodiments, q is 1-4. In someembodiments, q is 1. In some embodiments, q is 2. In some embodiments, qis 3. In some embodiments, q is 4.

In some embodiments, each of p and q is independently 1-4. In someembodiments, p is 2 and q is 2. In some embodiments, p is 2 and q is 2,and each of Ring C and Ring D independently has two substituents. Insome embodiments, each of Ring C and Ring D has two substituents, andeach substituent is at the o-position relative to the ring atom bondedto Ring B.

As generally defined above, each of Ring C and Ring D is independentlyan optionally substituted 5-membered monocyclic heteroaryl ring having1-4 nitrogen atoms. In some embodiments, each of Ring C and Ring D isindependently an optionally substituted group selected from pyrrolyl,imidazolyl, and pyrazolyl.

In some embodiments, at least one of Ring C and Ring D is a2,5-disubstituted 5-membered monocyclic heteroaryl ring having 1-4nitrogen atoms. In some embodiments, at least one of Ring C and Ring Dis a 2,5-disubstituted 5-membered monocyclic heteroaryl ring having 1-4nitrogen atoms. In some embodiments, each of Ring C and Ring D is adisubstituted 5-membered monocyclic heteroaryl ring having 1-4 nitrogenatoms. In some embodiments, each of Ring C and Ring D is a2,5-disubstituted 5-membered monocyclic heteroaryl ring having 1-4nitrogen atoms.

In some embodiments, at least one of Ring C and Ring D is optionallysubstituted pyrrolyl. In some embodiments, at least one of Ring C andRing D is independently optionally substituted pyrrolyl having thestructure of

wherein each of p, q, R^(y) and R^(z) is independently as defined aboveand described herein. In some embodiments, at least one of Ring C andRing D is disubstituted pyrrolyl having the structure of

wherein each of R^(y) and R^(z) is independently as defined above anddescribed herein. In some embodiments, at least one of Ring C and Ring Dis 2,5-disubstituted pyrrolyl. In some embodiments, at least one of RingC and Ring D is 2,5-disubstituted pyrrolyl having the structure of

wherein each of R^(y) and R^(z) is independently as defined above anddescribed herein. In some embodiments, at least one of Ring C and Ring Dis

wherein each of the phenyl and isopropyl group is independentlyoptionally substituted. In some embodiments, at least one of Ring C andRing D is

In some embodiments, at least one of Ring C and Ring D is

In some embodiments, at least one of Ring C and Ring D is

In some embodiments, each of Ring C and Ring D is independentlyoptionally substituted pyrrolyl. In some embodiments, each of Ring C andRing D is independently disubstituted pyrrolyl. In some embodiments,Ring C has the structure of

and Ring D has the structure of

wherein each of R^(y) and R^(z) is independently as defined above anddescribed herein. In some embodiments, each of Ring C and Ring D isindependently 2,5-disubstituted pyrrolyl. In some embodiments, Ring Chas the structure of

and Ring D has the structure of

wherein each of R^(y) and R^(z) is independently as defined above anddescribed herein. In some embodiments, each of Ring C and Ring D isindependently

wherein each of the phenyl, isopropyl and pyrrolyl groups isindependently optionally substituted. In some embodiments, each of RingC and Ring D is independently

In some embodiments, each of Ring C and Ring D is

In some embodiments, each of Ring C and Ring D is

wherein each phenyl group is optionally substituted. In someembodiments, each of Ring C and Ring D is

In some embodiments, Ring C is an optionally substituted 5-memberedmonocyclic heteroaryl ring having 1-4 nitrogen atoms. In someembodiments, Ring C is an optionally substituted 5-membered monocyclicheteroaryl ring having one nitrogen atom. In some embodiments, Ring C isoptionally substituted pyrrolyl. In some embodiments, Ring C isoptionally substituted 1-pyrrolyl. In some embodiments, Ring C is anoptionally substituted 5-membered monocyclic heteroaryl ring having twonitrogen atoms. In some embodiments, Ring C is optionally substitutedimidazolyl. In some embodiments, Ring C is optionally substitutedpyrazolyl. In some embodiments, Ring C is an optionally substituted5-membered monocyclic heteroaryl ring having three nitrogen atoms. Insome embodiments, Ring C is optionally substituted triazolyl. In someembodiments, Ring C is an optionally substituted 5-membered monocyclicheteroaryl ring having four nitrogen atoms. In some embodiments, Ring Cis optionally substituted tetrazolyl.

In some embodiments, Ring C is optionally substituted pyrrolyl. In someembodiments, Ring C is optionally substituted 1-pyrrolyl. In someembodiments, Ring C is optionally substituted pyrrolyl having thestructure of

wherein each of p and R^(y) is independently as defined above anddescribed herein. In some embodiments, Ring C is

In some embodiments, Ring C is tetrasubstituted. In some embodiments,Ring C is disubstituted pyrrolyl. In some embodiments, Ring C isdisubstituted pyrrolyl having the structure of

In some embodiments, Ring C is 2,5-disubstituted pyrrolyl. In someembodiments, Ring C is 2,5-disubstituted pyrrolyl having the structureof

In some embodiments, Ring C is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, Ring C is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, Ring C is optionally substituted imidazolyl. Insome embodiments, Ring C is optionally substituted imidazolyl having thestructure of

wherein each of p and R^(y) is independently as defined above anddescribed herein. In some embodiments, Ring C is disubstitutedimidazolyl. In some embodiments, Ring C is disubstituted imidazolylhaving the structure of

In some embodiments, Ring C is 2,5-disubstituted imidazolyl. In someembodiments, Ring C is 2,5-disubstituted imidazolyl having the structureof

In some embodiments, Ring C is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, Ring C is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, Ring C is optionally substituted pyrazolyl. In someembodiments, Ring C is optionally substituted pyrazolyl having thestructure of

wherein each of p and R^(y) is independently as defined above anddescribed herein. In some embodiments, Ring C is disubstitutedpyrazolyl. In some embodiments, Ring C is disubstituted pyrazolyl havingthe structure of

In some embodiments, Ring D is an optionally substituted 5-memberedmonocyclic heteroaryl ring having 1-4 nitrogen atoms. In someembodiments, Ring D is an optionally substituted 5-membered monocyclicheteroaryl ring having one nitrogen atom. In some embodiments, Ring D isoptionally substituted pyrrolyl. In some embodiments, Ring D isoptionally substituted 1-pyrrolyl. In some embodiments, Ring D is anoptionally substituted 5-membered monocyclic heteroaryl ring having twonitrogen atoms. In some embodiments, Ring D is optionally substitutedimidazolyl. In some embodiments, Ring D is optionally substitutedpyrazolyl. In some embodiments, Ring D is an optionally substituted5-membered monocyclic heteroaryl ring having three nitrogen atoms. Insome embodiments, Ring D is optionally substituted triazolyl. In someembodiments, Ring D is an optionally substituted 5-membered monocyclicheteroaryl ring having four nitrogen atoms. In some embodiments, Ring Dis optionally substituted tetrazolyl.

In some embodiments, Ring D is optionally substituted pyrrolyl. In someembodiments, Ring D is optionally substituted 1-pyrrolyl. In someembodiments, Ring D is optionally substituted pyrrolyl having thestructure of

wherein each of p and R^(y) is independently as defined above anddescribed herein. In some embodiments, Ring D is

In some embodiments, Ring D is tetrasubstituted. In some embodiments,Ring D is disubstituted pyrrolyl. In some embodiments, Ring D isdisubstituted pyrrolyl. In some embodiments, Ring D is disubstitutedpyrrolyl having the structure of

In some embodiments, Ring D is 2,5-disubstituted pyrrolyl. In someembodiments, Ring D is 2,5-disubstituted pyrrolyl having the structureof

In some embodiments, Ring D is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, Ring D is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, Ring D is optionally substituted imidazolyl. Insome embodiments, Ring D is optionally substituted imidazolyl having thestructure of

wherein each of p and R^(y) is independently as defined above anddescribed herein. In some embodiments, Ring D is disubstitutedimidazolyl. In some embodiments, Ring D is disubstituted imidazolylhaving the structure of

In some embodiments, Ring D is 2,5-disubstituted imidazolyl. In someembodiments, Ring D is 2,5-disubstituted imidazolyl having the structureof

In some embodiments, Ring D is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, Ring D is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, Ring D is optionally substituted pyrazolyl. In someembodiments, Ring D is optionally substituted pyrazolyl having thestructure of

wherein each of p and R^(y) is independently as defined above anddescribed herein. In some embodiments, Ring D is disubstitutedpyrazolyl. In some embodiments, Ring D is disubstituted pyrazolyl havingthe structure of

In some embodiments, Ring C and Ring D are the same. In someembodiments, Ring C and Ring D are different. In some embodiments, RingC and Ring D are different, and at least one of Ring C and Ring D isoptionally substituted pyrrolyl.

As generally defined above, each of R^(x), R^(y) and R^(z) isindependently halogen, —OR′, —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′,—NR′C(O)N(R′)₂, —NR′SO₂R′, —NR′SO₂N(R′)₂, —NR′OR′, or an optionallysubstituted group selected from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatichaving 1-3 heteroatoms independently selected from nitrogen, oxygen, orsulfur, phenyl, a 3-7 membered saturated or partially unsaturatedcarbocyclic ring, an 8-10 membered bicyclic saturated, partiallyunsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ringhaving 1-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur, a 3-7 membered saturated or partially unsaturated heterocyclicring having 1-3 heteroatoms independently selected from nitrogen,oxygen, or sulfur, a 7-10 membered bicyclic saturated or partiallyunsaturated heterocyclic ring having 1-5 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclicheteroaryl ring having 1-5 heteroatoms independently selected fromnitrogen, oxygen, or sulfur.

In certain embodiments, R^(x) is independently halogen. In someembodiments, R^(x) is —F. In some embodiments, R^(x) is —Cl. In someembodiments, R^(x) is —Br. In some embodiments, R^(x) is —I.

In some embodiments, R^(x) is —OR′, —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′,—NR′C(O)N(R′)₂, —NR′SO₂R′, —NR′SO₂N(R′)₂, or —NR′OR′, wherein each of R′is independently as defined above and described herein.

In some embodiments, R^(x) is an optionally substituted group selectedfrom C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, phenyl, a 3-7membered saturated or partially unsaturated carbocyclic ring, an 8-10membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6membered monocyclic heteroaryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated orpartially unsaturated heterocyclic ring having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 7-10 memberedbicyclic saturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R^(x) is optionally substituted C₁₋₂₀ aliphatic. Insome embodiments, R^(x) is optionally substituted C₁₋₂₀ alkyl. In someembodiments, R^(x) is optionally substituted C₁₋₁₂ aliphatic. In someembodiments, R^(x) is optionally substituted C₁₋₁₂ alkyl. In someembodiments, R^(x) is optionally substituted C₁₋₆ aliphatic. In someembodiments, R^(x) is optionally substituted C₁₋₆ alkyl. In someembodiments, R^(x) is optionally substituted hexyl, pentyl, butyl,propyl, ethyl or methyl. In some embodiments, R^(x) is optionallysubstituted hexyl. In some embodiments, R^(x) is optionally substitutedpentyl. In some embodiments, R^(x) is optionally substituted butyl. Insome embodiments, R^(x) is optionally substituted propyl. In someembodiments, R^(x) is optionally substituted ethyl. In some embodiments,R^(x) is optionally substituted methyl. In some embodiments, R^(x) ishexyl. In some embodiments, R^(x) is pentyl. In some embodiments, R^(x)is butyl. In some embodiments, R^(x) is propyl. In some embodiments,R^(x) is ethyl. In some embodiments, R^(x) is methyl. In someembodiments, R^(x) is isopropyl.

In some embodiments, R^(x) optionally substituted C₁₋₂₀ heteroaliphatichaving 1-3 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R^(x) is —OR′, wherein R′ is as definedabove and described herein. In some embodiments, R^(x) is —SR′, whereinR′ is as defined above and described herein. In some embodiments, R^(x)is —N(R′)₂, wherein each R′ is independently as defined above anddescribed herein.

In some embodiments, R^(x) is R′, wherein R′ is as defined above anddescribed herein.

In some embodiments, R^(x) is optionally substituted phenyl. In someembodiments, R^(x) is optionally substituted phenyl wherein one or moresubstituents are halogen. In some embodiments, R^(x) is optionallysubstituted phenyl wherein one or more substituents are —F. In someembodiments, R^(x) is optionally substituted phenyl wherein one or moresubstituents are —Cl. In some embodiments, R^(x) is optionallysubstituted phenyl wherein one or more substituents are —Br. In someembodiments, R^(x) is optionally substituted phenyl wherein one or moresubstituents are —I. In some embodiments, R^(x) is phenyl.

In some embodiments, R^(x) is a 3-7 membered saturated or partiallyunsaturated carbocyclic ring. In some embodiments, R^(x) is a 3-memberedsaturated or partially unsaturated carbocyclic ring. In someembodiments, R^(x) is a 4-membered saturated or partially unsaturatedcarbocyclic ring. In some embodiments, R^(x) is a 5-membered saturatedor partially unsaturated carbocyclic ring. In some embodiments, R^(x) isa 6-membered saturated or partially unsaturated carbocyclic ring. Insome embodiments, R^(x) is a 7-membered saturated or partiallyunsaturated carbocyclic ring.

In some embodiments, R^(x) is an 8-10 membered bicyclic saturated,partially unsaturated or aryl ring. In some embodiments, R^(x) is an8-10 membered bicyclic saturated ring. In some embodiments, R^(x) is an8-10 membered bicyclic partially unsaturated ring. In some embodiments,R^(x) is an 8-10 membered bicyclic aryl ring.

In some embodiments, R^(x) is a 5-6 membered monocyclic heteroaryl ringhaving 1-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R^(x) is a 5-membered monocyclic heteroarylring having 1-4 heteroatoms independently selected from nitrogen,oxygen, or sulfur. In some embodiments, R^(x) is a 6-membered monocyclicheteroaryl ring having 1-4 heteroatoms independently selected fromnitrogen, oxygen, or sulfur.

In some embodiments, R^(x) is a 3-7 membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R^(x) isa 3-membered saturated or partially unsaturated heterocyclic ring having1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.In some embodiments, R^(x) is a 4-membered saturated or partiallyunsaturated heterocyclic ring having 1-2 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R^(x) isa 5-membered saturated or partially unsaturated heterocyclic ring having1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.In some embodiments, R^(x) is a 6-membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R^(x) isa 7-membered saturated or partially unsaturated heterocyclic ring having1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R^(x) is a 7-10 membered bicyclic saturated orpartially unsaturated heterocyclic ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R^(x) is an 8-10 membered bicyclic heteroaryl ringhaving 1-5 heteroatoms independently selected from nitrogen, oxygen, orsulfur.

In certain embodiments, R^(y) is independently halogen. In someembodiments, R^(y) is —F. In some embodiments, R^(y) is —Cl. In someembodiments, R^(y) is —Br. In some embodiments, R^(y) is —I.

In some embodiments, R^(y) is —OR′, —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′,—NR′C(O)N(R′)₂, —NR′SO₂R′, —NR′SO₂N(R′)₂, or —NR′OR′, wherein each of R′is independently as defined above and described herein.

In some embodiments, R^(y) is an optionally substituted group selectedfrom C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, phenyl, a 3-7membered saturated or partially unsaturated carbocyclic ring, an 8-10membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6membered monocyclic heteroaryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated orpartially unsaturated heterocyclic ring having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 7-10 memberedbicyclic saturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R^(y) is optionally substituted C₁₋₂₀ aliphatic. Insome embodiments, R^(y) is optionally substituted C₁₋₂₀ alkyl. In someembodiments, R^(y) is optionally substituted C₁₋₁₂ aliphatic. In someembodiments, R^(y) is optionally substituted C₁₋₁₂ alkyl. In someembodiments, R^(y) is optionally substituted C₁₋₆ aliphatic. In someembodiments, R^(y) is optionally substituted C₁₋₆ alkyl. In someembodiments, R^(y) is optionally substituted hexyl, pentyl, butyl,propyl, ethyl or methyl. In some embodiments, R^(y) is optionallysubstituted hexyl. In some embodiments, R^(y) is optionally substitutedpentyl. In some embodiments, R^(y) is optionally substituted butyl. Insome embodiments, R^(y) is optionally substituted propyl. In someembodiments, R^(y) is optionally substituted ethyl. In some embodiments,R^(y) is optionally substituted methyl. In some embodiments, R^(y) ishexyl. In some embodiments, R^(y) is pentyl. In some embodiments, R^(y)is butyl. In some embodiments, R^(y) is propyl. In some embodiments,R^(y) is ethyl. In some embodiments, R^(y) is methyl. In someembodiments, R^(y) is isopropyl.

In some embodiments, R^(y) optionally substituted C₁₋₂₀ heteroaliphatichaving 1-3 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R^(y) is —OR′, wherein R′ is as definedabove and described herein. In some embodiments, R^(y) is —SR′, whereinR′ is as defined above and described herein. In some embodiments, R^(y)is —N(R′)₂, wherein each R′ is independently as defined above anddescribed herein.

In some embodiments, R^(y) is R′, wherein R′ is as defined above anddescribed herein.

In some embodiments, R^(y) is optionally substituted phenyl. In someembodiments, R^(y) is optionally substituted phenyl wherein one or moresubstituents are halogen. In some embodiments, R^(y) is optionallysubstituted phenyl wherein one or more substituents are —F. In someembodiments, R^(y) is optionally substituted phenyl wherein one or moresubstituents are —Cl. In some embodiments, R^(y) is optionallysubstituted phenyl wherein one or more substituents are —Br. In someembodiments, R^(y) is optionally substituted phenyl wherein one or moresubstituents are —I. In some embodiments, R^(y) is phenyl.

In some embodiments, R^(y) is a 3-7 membered saturated or partiallyunsaturated carbocyclic ring. In some embodiments, R^(y) is a 3-memberedsaturated or partially unsaturated carbocyclic ring. In someembodiments, R^(y) is a 4-membered saturated or partially unsaturatedcarbocyclic ring. In some embodiments, R^(y) is a 5-membered saturatedor partially unsaturated carbocyclic ring. In some embodiments, R^(y) isa 6-membered saturated or partially unsaturated carbocyclic ring. Insome embodiments, R^(y) is a 7-membered saturated or partiallyunsaturated carbocyclic ring.

In some embodiments, R^(y) is an 8-10 membered bicyclic saturated,partially unsaturated or aryl ring. In some embodiments, R^(y) is an8-10 membered bicyclic saturated ring. In some embodiments, R^(y) is an8-10 membered bicyclic partially unsaturated ring. In some embodiments,R^(y) is an 8-10 membered bicyclic aryl ring.

In some embodiments, R^(y) is a 5-6 membered monocyclic heteroaryl ringhaving 1-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R^(y) is a 5-membered monocyclic heteroarylring having 1-4 heteroatoms independently selected from nitrogen,oxygen, or sulfur. In some embodiments, R^(y) is a 6-membered monocyclicheteroaryl ring having 1-4 heteroatoms independently selected fromnitrogen, oxygen, or sulfur.

In some embodiments, R^(y) is a 3-7 membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R^(y) isa 3-membered saturated or partially unsaturated heterocyclic ring having1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.In some embodiments, R^(y) is a 4-membered saturated or partiallyunsaturated heterocyclic ring having 1-2 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R^(y) isa 5-membered saturated or partially unsaturated heterocyclic ring having1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.In some embodiments, R^(y) is a 6-membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R^(y) isa 7-membered saturated or partially unsaturated heterocyclic ring having1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R^(y) is a 7-10 membered bicyclic saturated orpartially unsaturated heterocyclic ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R^(y) is an 8-10 membered bicyclic heteroaryl ringhaving 1-5 heteroatoms independently selected from nitrogen, oxygen, orsulfur.

In certain embodiments, R^(z) is independently halogen. In someembodiments, R^(z) is —F. In some embodiments, R^(z) is —Cl. In someembodiments, R^(z) is —Br. In some embodiments, R^(z) is —I.

In some embodiments, R^(z) is —OR′, —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′,—NR′C(O)N(R′)₂, —NR′SO₂R′, —NR′SO₂N(R′)₂, or —NR′OR′, wherein each of R′is independently as defined above and described herein.

In some embodiments, R^(z) is an optionally substituted group selectedfrom C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, phenyl, a 3-7membered saturated or partially unsaturated carbocyclic ring, an 8-10membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6membered monocyclic heteroaryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated orpartially unsaturated heterocyclic ring having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 7-10 memberedbicyclic saturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R^(z) is optionally substituted C₁₋₂₀ aliphatic. Insome embodiments, R^(z) is optionally substituted C₁₋₂₀ alkyl. In someembodiments, R^(z) is optionally substituted C₁₋₁₂ aliphatic. In someembodiments, R^(z) is optionally substituted C₁₋₁₂ alkyl. In someembodiments, R^(z) is optionally substituted C₁₋₆ aliphatic. In someembodiments, R^(z) is optionally substituted C₁₋₆ alkyl. In someembodiments, R^(z) is optionally substituted hexyl, pentyl, butyl,propyl, ethyl or methyl. In some embodiments, R^(z) is optionallysubstituted hexyl. In some embodiments, R^(z) is optionally substitutedpentyl. In some embodiments, R^(z) is optionally substituted butyl. Insome embodiments, R^(z) is optionally substituted propyl. In someembodiments, R^(z) is optionally substituted ethyl. In some embodiments,R^(z) is optionally substituted methyl. In some embodiments, R^(z) ishexyl. In some embodiments, R^(z) is pentyl. In some embodiments, R^(z)is butyl. In some embodiments, R^(z) is propyl. In some embodiments,R^(z) is ethyl. In some embodiments, R^(z) is methyl. In someembodiments, R^(z) is isopropyl.

In some embodiments, R^(z) optionally substituted C₁₋₂₀ heteroaliphatichaving 1-3 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R^(z) is —OR′, wherein R′ is as definedabove and described herein. In some embodiments, R^(z) is —SR′, whereinR′ is as defined above and described herein. In some embodiments, R^(z)is —N(R′)₂, wherein each R′ is independently as defined above anddescribed herein.

In some embodiments, R^(z) is R′, wherein R′ is as defined above anddescribed herein.

In some embodiments, R^(z) is optionally substituted phenyl. In someembodiments, R^(z) is optionally substituted phenyl wherein one or moresubstituents are halogen. In some embodiments, R^(z) is optionallysubstituted phenyl wherein one or more substituents are —F. In someembodiments, R^(z) is optionally substituted phenyl wherein one or moresubstituents are —Cl. In some embodiments, R^(z) is optionallysubstituted phenyl wherein one or more substituents are —Br. In someembodiments, R^(z) is optionally substituted phenyl wherein one or moresubstituents are —I. In some embodiments, R^(z) is phenyl.

In some embodiments, R^(z) is a 3-7 membered saturated or partiallyunsaturated carbocyclic ring. In some embodiments, R^(z) is a 3-memberedsaturated or partially unsaturated carbocyclic ring. In someembodiments, R^(z) is a 4-membered saturated or partially unsaturatedcarbocyclic ring. In some embodiments, R^(z) is a 5-membered saturatedor partially unsaturated carbocyclic ring. In some embodiments, R^(z) isa 6-membered saturated or partially unsaturated carbocyclic ring. Insome embodiments, R^(z) is a 7-membered saturated or partiallyunsaturated carbocyclic ring.

In some embodiments, R^(z) is an 8-10 membered bicyclic saturated,partially unsaturated or aryl ring. In some embodiments, R^(z) is an8-10 membered bicyclic saturated ring. In some embodiments, R^(z) is an8-10 membered bicyclic partially unsaturated ring. In some embodiments,R^(z) is an 8-10 membered bicyclic aryl ring.

In some embodiments, R^(z) is a 5-6 membered monocyclic heteroaryl ringhaving 1-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R^(z) is a 5-membered monocyclic heteroarylring having 1-4 heteroatoms independently selected from nitrogen,oxygen, or sulfur. In some embodiments, R^(z) is a 6-membered monocyclicheteroaryl ring having 1-4 heteroatoms independently selected fromnitrogen, oxygen, or sulfur.

In some embodiments, R^(z) is a 3-7 membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur.

In some embodiments, R^(z) is a 7-10 membered bicyclic saturated orpartially unsaturated heterocyclic ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur. In someembodiments, R^(z) is a 3-membered saturated or partially unsaturatedheterocyclic ring having 1-2 heteroatoms independently selected fromnitrogen, oxygen, or sulfur. In some embodiments, R^(z) is a 4-memberedsaturated or partially unsaturated heterocyclic ring having 1-2heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R^(z) is a 5-membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R^(z) isa 6-membered saturated or partially unsaturated heterocyclic ring having1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.In some embodiments, R^(z) is a 7-membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur.

In some embodiments, R^(z) is an 8-10 membered bicyclic heteroaryl ringhaving 1-5 heteroatoms independently selected from nitrogen, oxygen, orsulfur.

In some embodiments, each of R^(y) and R^(z) is independently anoptionally substituted group selected from C₁₋₂₀ aliphatic, C₁₋₂₀heteroaliphatic having 1-3 heteroatoms independently selected fromnitrogen, oxygen, or sulfur, phenyl, a 3-7 membered saturated orpartially unsaturated carbocyclic ring, an 8-10 membered bicyclicsaturated, partially unsaturated or aryl ring, a 5-6 membered monocyclicheteroaryl ring having 1-4 heteroatoms independently selected fromnitrogen, oxygen, or sulfur, a 3-7 membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclicsaturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur. In someembodiments, each of R^(y) and R^(z) is independently an optionallysubstituted group selected from C₁₋₂₀ aliphatic, phenyl, an 8-10membered bicyclic aryl ring, a 5-6 membered monocyclic heteroaryl ringhaving 1-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, each of R^(y) and R^(z) is independently an optionallysubstituted group selected from C₁₋₂₀ aliphatic, phenyl, and a 5-6membered monocyclic heteroaryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen. In some embodiments, each of R^(y) andR^(z) is independently an optionally substituted group selected fromC₁₋₂₀ aliphatic and phenyl.

In some embodiments, each R^(y) and R^(z) is independently R′, whereinR′ is as defined above and described herein.

In some embodiments, each of R^(y) and R^(z) is independently optionallysubstituted C₁₋₂₀ aliphatic. In some embodiments, each of R^(y) andR^(z) is independently optionally substituted C₁₋₁₂ aliphatic. In someembodiments, each of R^(y) and R^(z) is independently optionallysubstituted C₁₋₆ aliphatic. In some embodiments, each of R^(y) and R^(z)is independently optionally substituted C₁₋₆ alkyl. In some embodiments,each of R^(y) and R^(z) is independently optionally substituted hexyl.In some embodiments, each of R^(y) and R^(z) is independently optionallysubstituted pentyl. In some embodiments, each of R^(y) and R^(z) isindependently optionally substituted butyl. In some embodiments, each ofR^(y) and R^(z) is independently optionally substituted propyl. In someembodiments, each of R^(y) and R^(z) is independently optionallysubstituted ethyl. In some embodiments, each of R^(y) and R^(z) isindependently optionally substituted methyl. In some embodiments, eachof R^(y) and R^(z) is hexyl. In some embodiments, each of R^(y) andR^(z) is pentyl. In some embodiments, each of R^(y) and R^(z) is butyl.In some embodiments, each of R^(y) and R^(z) is propyl. In someembodiments, each of R^(y) and R^(z) is ethyl. In some embodiments, eachof R^(y) and R^(z) is methyl. In some embodiments, each of R^(y) andR^(z) is isopropyl.

In some embodiments, each of R^(y) and R^(z) is independently optionallysubstituted phenyl. In some embodiments, each of R^(y) and R^(z) isindependently phenyl.

As generally defined above, each R′ is independently hydrogen or anoptionally substituted group selected from C₁₋₆ aliphatic, phenyl, a 3-7membered saturated or partially unsaturated carbocyclic ring, an 8-10membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6membered monocyclic heteroaryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated orpartially unsaturated heterocyclic ring having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 7-10 memberedbicyclic saturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur; or:

-   -   two R′ groups on the same nitrogen atom are optionally taken        together with the nitrogen atom to form an optionally        substituted 3-8 membered, saturated, partially unsaturated, or        aryl ring having 1-4 heteroatoms independently selected from        nitrogen, oxygen, or sulfur.

In some embodiments, R′ is hydrogen.

In some embodiments, R′ is an optionally substituted group selected fromC₁₋₆ aliphatic, phenyl, a 3-7 membered saturated or partiallyunsaturated carbocyclic ring, an 8-10 membered bicyclic saturated,partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroarylring having 1-4 heteroatoms independently selected from nitrogen,oxygen, or sulfur, a 3-7 membered saturated or partially unsaturatedheterocyclic ring having 1-3 heteroatoms independently selected fromnitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated orpartially unsaturated heterocyclic ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, or an 8-10membered bicyclic heteroaryl ring having 1-5 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, two R′groups on the same nitrogen atom are optionally taken together with thenitrogen atom to form an optionally substituted 3-8 membered, saturated,partially unsaturated, or aryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur.

In some embodiments, R′ is optionally substituted C₁₋₆ aliphatic. Insome embodiments, R′ is optionally substituted C₁₋₆ alkyl. In someembodiments, R′ is optionally substituted hexyl, pentyl, butyl, propyl,ethyl or methyl. In some embodiments, R′ is optionally substitutedhexyl. In some embodiments, R′ is optionally substituted pentyl. In someembodiments, R′ is optionally substituted butyl. In some embodiments, R′is optionally substituted propyl. In some embodiments, R′ is optionallysubstituted ethyl. In some embodiments, R′ is optionally substitutedmethyl. In some embodiments, R′ is hexyl. In some embodiments, R′ ispentyl. In some embodiments, R′ is butyl. In some embodiments, R′ ispropyl. In some embodiments, R′ is ethyl. In some embodiments, R′ ismethyl. In some embodiments, R′ is isopropyl. In some embodiments, R′ istert-butyl. In some embodiments, R′ is —C(Me)₂Ph.

In some embodiments, R′ is optionally substituted phenyl. In someembodiments, R′ is optionally substituted phenyl wherein one or moresubstituents are halogen. In some embodiments, R′ is optionallysubstituted phenyl wherein one or more substituents are —F. In someembodiments, R′ is optionally substituted phenyl wherein one or moresubstituents are —Cl. In some embodiments, R′ is optionally substitutedphenyl wherein one or more substituents are —Br. In some embodiments, R′is optionally substituted phenyl wherein one or more substituents are—I. In some embodiments, R′ is phenyl.

In some embodiments, R′ is a 3-7 membered saturated or partiallyunsaturated carbocyclic ring. In some embodiments, R′ is a 3-memberedsaturated or partially unsaturated carbocyclic ring. In someembodiments, R′ is a 4-membered saturated or partially unsaturatedcarbocyclic ring. In some embodiments, R′ is a 5-membered saturated orpartially unsaturated carbocyclic ring. In some embodiments, R′ is a6-membered saturated or partially unsaturated carbocyclic ring. In someembodiments, R′ is a 7-membered saturated or partially unsaturatedcarbocyclic ring. In some embodiments, R′ is an optionally substitutedcycloheptyl. In some embodiments, R′ is an optionally substitutedcyclohexyl. In some embodiments, R′ is an optionally substitutedcyclopentyl. In some embodiments, R′ is an optionally substitutedcyclobutyl. In some embodiments, R′ is an optionally substitutedcyclopropyl.

In some embodiments, R′ is an 8-10 membered bicyclic saturated,partially unsaturated or aryl ring. In some embodiments, R′ is an 8-10membered bicyclic saturated ring. In some embodiments, R′ is an 8-10membered bicyclic partially unsaturated ring. In some embodiments, R′ isan 8-10 membered bicyclic aryl ring.

In some embodiments, R′ is a 5-6 membered monocyclic heteroaryl ringhaving 1-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R′ is a substituted 5-6 membered monocyclicheteroaryl ring having 1-3 heteroatoms independently selected fromnitrogen, oxygen, or sulfur. In some embodiments, R′ is an unsubstituted5-6 membered monocyclic heteroaryl ring having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur. In someembodiments, R′ is a 5-membered monocyclic heteroaryl ring having 1-4heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R′ is a 6-membered monocyclic heteroaryl ring having1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R′ is an optionally substituted 5-memberedmonocyclic heteroaryl ring having 1-3 heteroatoms independently selectedfrom nitrogen, oxygen or sulfur. In some embodiments, R′ is anoptionally substituted 6-membered monocyclic heteroaryl ring having 1-3heteroatoms independently selected from nitrogen, oxygen, or sulfur.

In some embodiments, R′ is an optionally substituted 5-memberedmonocyclic heteroaryl ring having 1 heteroatom selected from nitrogen,oxygen, or sulfur. In some embodiments, R′ is selected from pyrrolyl,furanyl, or thienyl.

In some embodiments, R′ is an optionally substituted 5-memberedheteroaryl ring having two heteroatoms independently selected fromnitrogen, oxygen, or sulfur. In certain embodiments, R′ is an optionallysubstituted 5-membered heteroaryl ring having one nitrogen atom, and anadditional heteroatom selected from sulfur or oxygen. Exemplary R′groups include optionally substituted pyrazolyl, imidazolyl, thiazolyl,isothiazolyl, oxazolyl or isoxazolyl.

In some embodiments, R′ is a 6-membered heteroaryl ring having 1-3nitrogen atoms. In other embodiments, R′ is an optionally substituted6-membered heteroaryl ring having 1-2 nitrogen atoms. In someembodiments, R′ is an optionally substituted 6-membered heteroaryl ringhaving two nitrogen atoms. In certain embodiments, R′ is an optionallysubstituted 6-membered heteroaryl ring having one nitrogen atom.Exemplary R′ groups include optionally substituted pyridinyl,pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, or tetrazinyl.

In some embodiments, R′ is an optionally substituted 3-7 memberedsaturated or partially unsaturated heterocyclic ring having 1-2heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R′ is a substituted 3-7 membered saturated orpartially unsaturated heterocyclic ring having 1-2 heteroatomsindependently selected from nitrogen, oxygen, or sulfur. In someembodiments, R′ is an unsubstituted 3-7 membered saturated or partiallyunsaturated heterocyclic ring having 1-2 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur.

In certain embodiments, R′ is an optionally substituted 5-6 memberedpartially unsaturated monocyclic ring having 1-2 heteroatomsindependently selected from nitrogen, oxygen, or sulfur. In certainembodiments, R′ is an optionally substituted tetrahydropyridinyl,dihydrothiazolyl, dihydrooxazolyl, or oxazolinyl group.

In some embodiments, R′ is an optionally substituted 6-memberedsaturated or partially unsaturated heterocyclic ring having 1-2heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R′ is an optionally substituted 6-membered partiallyunsaturated heterocyclic ring having 2 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R′ is anoptionally substituted 6-membered partially unsaturated heterocyclicring having 2 oxygen atom.

In certain embodiments, R′ is an optionally substituted 5-6 memberedpartially unsaturated monocyclic ring having 1-2 heteroatomsindependently selected from nitrogen, oxygen, or sulfur. In certainembodiments, R′ is an optionally substituted tetrahydropyridinyl,dihydrothiazolyl, dihydrooxazolyl, or oxazolinyl group.

In certain embodiments, R′ is optionally substituted oxiranyl, oxetanyl,tetrahydrofuranyl, tetrahydropyranyl, oxepaneyl, aziridineyl,azetidineyl, pyrrolidinyl, piperidinyl, azepanyl, thiiranyl, thietanyl,tetrahydrothiophenyl, tetrahydrothiopyranyl, thiepanyl, dioxolanyl,oxathiolanyl, oxazolidinyl, imidazolidinyl, thiazolidinyl, dithiolanyl,dioxanyl, morpholinyl, oxathianyl, piperazinyl, thiomorpholinyl,dithianyl, dioxepanyl, oxazepanyl, oxathiepanyl, dithiepanyl,diazepanyl, dihydrofuranonyl, tetrahydropyranonyl, oxepanonyl,pyrrolidinonyl, piperidinonyl, azepanonyl, dihydrothiophenonyl,tetrahydrothiopyranonyl, thiepanonyl, oxazolidinonyl, oxazinanonyl,oxazepanonyl, dioxolanonyl, dioxanonyl, dioxepanonyl, oxathiolinonyl,oxathianonyl, oxathiepanonyl, thiazolidinonyl, thiazinanonyl,thiazepanonyl, imidazolidinonyl, tetrahydropyrimidinonyl, diazepanonyl,imidazolidinedionyl, oxazolidinedionyl, thiazolidinedionyl,dioxolanedionyl, oxathiolanedionyl, piperazinedionyl, morpholinedionyl,thiomorpholinedionyl, tetrahydropyranyl, tetrahydrofuranyl, morpholinyl,thiomorpholinyl, piperidinyl, piperazinyl, pyrrolidinyl,tetrahydrothiophenyl, or tetrahydrothiopyranyl.

In some embodiments, R′ is a 7-10 membered bicyclic saturated orpartially unsaturated heterocyclic ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur. In someembodiments, R′ is an optionally substituted indolinyl. In someembodiments, R′ is an optionally substituted isoindolinyl. In someembodiments, R′ is an optionally substituted1,2,3,4-tetrahydroquinoline. In some embodiments, R′ is an optionallysubstituted 1,2,3,4-tetrahydroisoquinoline.

In some embodiments, R′ is an 8-10 membered bicyclic heteroaryl ringhaving 1-5 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R′ is an optionally substituted 5,6-fusedheteroaryl ring having 1-5 heteroatoms independently selected fromnitrogen, oxygen, or sulfur. In other embodiments, R′ is an optionallysubstituted 5,6-fused heteroaryl ring having 1-2 heteroatomsindependently selected from nitrogen, oxygen, or sulfur. In certainembodiments, R′ is an optionally substituted 5,6-fused heteroaryl ringhaving 1 heteroatom independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R′ is an optionally substituted indolyl. Insome embodiments, R′ is an optionally substitutedazabicyclo[3.2.1]octanyl. In certain embodiments, R′ is an optionallysubstituted 5,6-fused heteroaryl ring having 2 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R′ is anoptionally substituted azaindolyl. In some embodiments, R′ is anoptionally substituted benzimidazolyl. In some embodiments, R′ is anoptionally substituted benzothiazolyl. In some embodiments, R′ is anoptionally substituted benzoxazolyl. In some embodiments, R′ is anoptionally substituted indazolyl. In certain embodiments, R′ is anoptionally substituted 5,6-fused heteroaryl ring having 3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur.

In certain embodiments, R′ is an optionally substituted 6,6-fusedheteroaryl ring having 1-4 heteroatoms independently selected fromnitrogen, oxygen, or sulfur. In some embodiments, R′ is an optionallysubstituted 6,6-fused heteroaryl ring having 1-2 heteroatomsindependently selected from nitrogen, oxygen, or sulfur. In otherembodiments, R′ is an optionally substituted 6,6-fused heteroaryl ringhaving 1 heteroatom independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R′ is an optionally substituted quinolinyl.In some embodiments, R′ is an optionally substituted isoquinolinyl.According to one aspect, R′ is an optionally substituted 6,6-fusedheteroaryl ring having 2 heteroatoms independently selected fromnitrogen, oxygen, or sulfur. In some embodiments, R′ is a quinazoline ora quinoxaline.

In some embodiments, each of R^(x), R^(y), and R^(z) is independentlyR′, wherein R′ is as defined above and described herein and is nothydrogen. In some embodiments, R^(x) is R′, wherein R′ is as definedabove and described herein and R′ is not hydrogen. In some embodiments,R^(y) is R′, wherein R′ is as defined above and described herein and R′is not hydrogen. In some embodiments, R^(z) is R′, wherein R′ is asdefined above and described herein and R′ is not hydrogen.

In some embodiments,

has the structure of:

wherein each variable is independently as defined above and describedherein.

In some embodiments,

has the structure of:

wherein each variable is independently as defined above and describedherein.

In some embodiments,

has the structure of:

wherein each variable is independently as defined above and describedherein.

In some embodiments,

has the structure of:

wherein each variable is independently as defined above and describedherein.

In some embodiments,

has the structure of:

wherein each variable is independently as defined above and describedherein.

In some embodiments,

has the structure of:

wherein each variable is independently as defined above and describedherein.

In some embodiments,

has the structure of:

wherein each variable is independently as defined above and describedherein.

In some embodiments,

has the structure of:

wherein each variable is independently as defined above and describedherein.

As defined generally above, R⁴ is an optionally substituted 5-memberedmonocyclic heteroaryl ring having 1-2 nitrogen atoms. In someembodiments, R⁴ is an optionally substituted 5-membered monocyclicheteroaryl ring having 1-2 nitrogen atoms, wherein R⁴ is bonded to Mthrough a nitrogen atom.

In some embodiments, R⁴ is an optionally substituted 5-memberedmonocyclic heteroaryl ring having 1-2 nitrogen atoms. In someembodiments, R⁴ is an optionally substituted 5-membered monocyclicheteroaryl ring having one nitrogen atom. In some embodiments, R⁴ isoptionally substituted pyrrolyl. In some embodiments, R⁴ is optionallysubstituted 1-pyrrolyl. In some embodiments, R⁴ is an optionallysubstituted 5-membered monocyclic heteroaryl ring having two nitrogenatoms. In some embodiments, R⁴ is optionally substituted imidazolyl. Insome embodiments, R⁴ is optionally substituted pyrazolyl.

In some embodiments, R⁴ is optionally substituted pyrrolyl. In someembodiments, R⁴ is optionally substituted 1-pyrrolyl. In someembodiments, R⁴ is optionally substituted pyrrolyl having the structureof

wherein each of p and R^(y) is independently as defined above anddescribed herein. In some embodiments, R⁴ is disubstituted pyrrolyl. Insome embodiments, R⁴ is disubstituted pyrrolyl having the structure of

In some embodiments, R⁴ is 2,5-disubstituted pyrrolyl. In someembodiments, R⁴ is 2,5-disubstituted pyrrolyl having the structure of

In some embodiments, R⁴ is 2,5-disubstituted pyrrolyl having thestructure of

wherein each R^(y) is independently R′. In some embodiments, R⁴ is2,5-disubstituted pyrrolyl having the structure of

wherein each R^(y) is independently hydrogen or C₁₋₄ aliphatic. In someembodiments, R⁴ is 2,5-disubstituted pyrrolyl having the structure of

In some embodiments, R⁴ is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, R⁴ is

In some embodiments, R⁴ is

In some embodiments, R⁴ is optionally substituted imidazolyl. In someembodiments, R⁴ is optionally substituted imidazolyl having thestructure of

wherein each of p and R^(y) is independently as defined above anddescribed herein. In some embodiments, R⁴ is disubstituted imidazolyl.In some embodiments, R⁴ is disubstituted imidazolyl having the structureof

In some embodiments, R⁴ is 2,5-disubstituted imidazolyl. In someembodiments, R⁴ is 2,5-disubstituted imidazolyl having the structure of

In some embodiments, R⁴ is 2,5-disubstituted pyrrolyl having thestructure of

wherein each R^(y) is independently R′. In some embodiments, R⁴ is2,5-disubstituted pyrrolyl having the structure of

wherein each R^(y) is independently hydrogen or C₁₋₄ aliphatic. In someembodiments, R⁴ is 2,5-disubstituted pyrrolyl having the structure of

In some embodiments, R⁴ is 2,5-disubstituted pyrrolyl having thestructure of

In some embodiments, R⁴ is optionally substituted pyrazolyl. In someembodiments, R⁴ is optionally substituted pyrazolyl having the structureof

wherein each of p and R^(y) is independently as defined above anddescribed herein. In some embodiments, R⁴ is disubstituted pyrazolyl. Insome embodiments, R⁴ is disubstituted pyrazolyl having the structure of

As defined above and described herein, R^(2′) and R^(3′) are takentogether with the intervening metal atom to form an optionallysubstituted 3-8 membered saturated or partially unsaturated ring having,in addition to the intervening metal atom, 0-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur. In some embodiments, R^(2′)and R^(3′) are taken together with the intervening metal atom to form anoptionally substituted 3-8 membered saturated or partially unsaturatedring, wherein each ring atom is either M or carbon.

In some embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 3-8 memberedsaturated ring having, in addition to the intervening metal atom, 0-4heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 3-8 memberedsaturated ring having, in addition to the intervening metal atom, 0-2heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 5-6 memberedsaturated ring having, in addition to the intervening metal atom, 0-4heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 5-6 memberedsaturated ring having, in addition to the intervening metal atom, 0-2heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 3-4 memberedsaturated ring having, in addition to the intervening metal atom, 0-4heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 3-4 memberedsaturated ring having, in addition to the intervening metal atom, 0-2heteroatoms independently selected from nitrogen, oxygen, or sulfur. Insome embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 3-5 memberedsaturated ring, wherein each ring atom is either M or carbon.

In some embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 3-memberedsaturated ring. In certain embodiments, R^(2′) and R^(3′) are takentogether with the intervening metal atom to form a substituted3-membered saturated ring. In certain embodiments, R^(2′) and R^(3′) aretaken together with the intervening metal atom to form a 3-memberedsaturated ring unsubstituted at the ring carbon atoms. In certainembodiments, R^(2′) and R^(3′) are taken together with the interveningmetal atom to form a metallacyclopropane ring optionally substituted atthe ring carbon atoms. In certain embodiments, R^(2′) and R^(3′) aretaken together with the intervening metal atom to formmetallacyclopropane, wherein the ring carbon atoms of themetallacyclobutane are not substituted. In some embodiments, a compoundof formula II wherein R^(2′) and R^(3′) are taken together with theintervening metal atom to form a metallacyclopropane ring can beconsidered as a compound comprising an olefin ligand. For example, a

moiety may be considered as

In certain embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 4-memberedsaturated ring. In certain embodiments, R^(2′) and R^(3′) are takentogether with the intervening metal atom to form a substituted4-membered saturated ring. In certain embodiments, R^(2′) and R^(3′) aretaken together with the intervening metal atom to form an unsubstituted4-membered saturated ring. In certain embodiments, R^(2′) and R^(3′) aretaken together with the intervening metal atom to formmetallacyclobutane optionally substituted at the ring carbon atoms. Incertain embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form metallacyclobutane, wherein the ringcarbon atoms of the metallacyclobutane are not substituted.

In some embodiments, a compound of formula II has the structure offormula II-a:

wherein each variable is independently as defined above and describedherein.

In certain embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 5-memberedsaturated ring. In certain embodiments, R^(2′) and R^(3′) are takentogether with the intervening metal atom to form a substituted5-membered saturated ring. In certain embodiments, R^(2′) and R^(3′) aretaken together with the intervening metal atom to form a 5-memberedsaturated ring unsubstituted at the ring carbon atoms. In certainembodiments, R^(2′) and R^(3′) are taken together with the interveningmetal atom to form a metallacyclopentane ring optionally substituted atthe ring carbon atoms. In certain embodiments, R^(2′) and R^(3′) aretaken together with the intervening metal atom to formmetallacyclopentane, wherein the ring carbon atoms of themetallacyclopentane are not substituted.

In some embodiments, R^(2′) and R^(3′) are taken together with theintervening metal atom to form an optionally substituted 3-8 memberedpartially unsaturated ring having, in addition to the intervening metalatom, 0-4 heteroatoms independently selected from nitrogen, oxygen, orsulfur. In some embodiments, R^(2′) and R^(3′) are taken together withthe intervening metal atom to form an optionally substituted 3-8membered partially unsaturated ring having, in addition to theintervening metal atom, 0-2 heteroatoms independently selected fromnitrogen, oxygen, or sulfur. In some embodiments, R^(2′) and R^(3′) aretaken together with the intervening metal atom to form an optionallysubstituted 5-6 membered partially unsaturated ring having, in additionto the intervening metal atom, 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur. In some embodiments, R^(2′) and R^(3′)are taken together with the intervening metal atom to form an optionallysubstituted 5-6 membered partially unsaturated ring having, in additionto the intervening metal atom, 0-2 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur. In some embodiments, R^(2′) and R^(3′)are taken together with the intervening metal atom to form an optionallysubstituted 3-4 membered partially unsaturated ring having, in additionto the intervening metal atom, 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur. In some embodiments, R^(2′) and R^(3′)are taken together with the intervening metal atom to form an optionallysubstituted 3-4 membered partially unsaturated ring having, in additionto the intervening metal atom, 0-2 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur.

In some embodiments, a compound of formula I has the structure offormula I-a:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula I has the structure offormula I-b:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula I has the structure offormula I-c:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula I has the structure offormula I-d:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula II has the structure offormula II-b:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula II has the structure offormula II-c:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula II has the structure offormula II-d:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula III has the structure offormula III-a:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula III has the structure offormula III-b:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula III has the structure offormula III-c:

wherein each variable is independently as defined above and describedherein.

In some embodiments, a compound of formula III has the structure offormula III-d:

wherein each variable is independently as defined above and describedherein.

Exemplary compounds of formula I include but are not limited to thosedepicted below:

In some embodiments, a compound of formula II is

Exemplary compounds of formula III include but are not limited to thosedepicted below:

Exemplary Uses of Provided Compounds

In some embodiments, a provided compound of formula III is used toprepare compounds that promote metathesis reactions. In someembodiments, a provided compound that promotes metathesis reactions hasthe structure of formula I. In some embodiments, a provided compoundthat promotes metathesis reactions has the structure of formula II.

In some embodiments, the present invention provides a method forpreparing a compound of formula I:

comprising:

-   -   (a) providing a first compound having the structure of formula        IV:

-   -   wherein each variable is independently as defined above and        described herein;    -   (b) providing a second compound having the structure of formula        III:

-   -   or its salt thereof;    -   wherein each variable is independently as defined above and        described herein; and    -   (c) reacting the first compound with the second compound.

In some embodiments, the present invention provides a method forpreparing a compound of formula II:

comprising:

-   -   (a) providing a first compound having the structure of formula        II:

-   -   (b) reacting the first compound with an olefin.        In some embodiments, an olefin is ethylene.

In some embodiments, the present invention provides methods forperforming highly efficient and Z-selection metathesis reactions. Insome embodiments, the present invention provides a method comprising:

-   -   (a) providing a compound of formula I or II;    -   (b) reacting a first unsaturated bond and a second unsaturated        bond to produce a product comprising an unsaturated bond;

In some embodiments, a compound in a provided method is a compound offormula I. In some embodiments, a compound in a provided method is acompound of formula II.

In some embodiments, a first unsaturated bond is an unsaturatedcarbon-carbon bond. In some embodiments, a second unsaturated bond is anunsaturated carbon-carbon bond. In some embodiments, both the first andthe second unsaturated bonds are unsaturated carbon-carbon bonds. Insome embodiments, a product comprising an unsaturated bond comprises anunsaturated carbon-carbon bond. In some embodiments, a productcomprising an unsaturated bond comprises an unsaturated carbon-carbonbond, wherein the unsaturated carbon-carbon bond comprises a carbon atomfrom the first unsaturated bond and a carbon atom from the secondunsaturated bond. In some embodiments, an unsaturated carbon-carbon bondis a double bond (C═C). In some embodiments, an unsaturatedcarbon-carbon bond is a triple bond (C≡C). In some embodiments, a firstunsaturated bond is a carbon-carbon double bond (C═C). In someembodiments, a first unsaturated bond is a carbon-carbon triple bond(C≡C). In some embodiments, a second unsaturated bond is a carbon-carbondouble bond (C═C). In some embodiments, a second unsaturated bond is acarbon-carbon triple bond (C≡C). In some embodiments, a productcomprising an unsaturated bond comprises an unsaturated carbon-carbonbond. In some embodiments, a product comprising an unsaturated bondcomprises a carbon-carbon double bond (C═C). In some embodiments, aproduct comprising an unsaturated bond comprises a carbon-carbon triplebond (C≡C). In some embodiments, both the first unsaturated bond and thesecond unsaturated bond are carbon-carbon double bond (C═C), and theproduct comprises a carbon-carbon double bond (C═C). In someembodiments, both the first unsaturated bond and the second unsaturatedbond are carbon-carbon double bond (C═C), and the product comprises acarbon-carbon double bond (C═C), wherein the carbon-carbon double bondin the product comprises a carbon atom from the first unsaturated bondand a carbon atom from the second unsaturated bonds. In someembodiments, a first unsaturated bond is a carbon-carbon double bond(C═C), a second unsaturated bond is a carbon-carbon triple bond (C≡C),and the product comprises a carbon-carbon double bond (C═C).

In some embodiments, the present invention provides a method comprising:

-   -   (a) providing a compound of formula I or II; and    -   (b) reacting a first unsaturated carbon-carbon bond and a second        unsaturated carbon-carbon bond to produce a product comprising        an unsaturated carbon-carbon bond, wherein said unsaturated        carbon-carbon bond in the product comprises one carbon atom from        the first unsaturated carbon-carbon bond and one carbon atom        from the second unsaturated carbon-carbon bond.

Highly efficient and Z-selective homocoupling of two olefins viametathesis reactions remains a major challenge in the field. Improvedefficiency and/or selectivity are highly desirable. In some embodiments,a provided compound is particularly efficient in promoting homocouplingmetathesis. In some embodiments, a provided compound is particularlyefficient in promoting the homocoupling of terminal alkenes. In someembodiments, a terminal alkene is 1-octene. In some embodiments, aprovided method comprising the use of a provided compound delivers up to62% conversion and >95% Z-selectivity in the homocoupling of 1-octene in10 minutes. Such high efficiency and selectivity are unexpected.

In some embodiments, the compound comprising the first unsaturatedcarbon-carbon bond and the compound comprising the second unsaturatedcarbon-carbon bond are identical. In some embodiments, the compoundcomprising the first unsaturated carbon-carbon bond is an olefin. Insome embodiments, the compound comprising the second unsaturatedcarbon-carbon bond is an olefin. In some embodiments, both the compoundcomprising the first unsaturated carbon-carbon bond and the compoundcomprising the second unsaturated carbon-carbon bond are olefin. In someembodiments, both the compound comprising the first unsaturatedcarbon-carbon bond and the compound comprising the second unsaturatedcarbon-carbon bond are olefin, and the two compounds are identical.

In some embodiments, the present invention provides exemplary compoundsand methods as follows:

E1. A compound of formula I:

wherein:

-   M is molybdenum or tungsten;-   R¹ is an optionally substituted group selected from C₁₋₂₀ aliphatic,    C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms independently selected    from nitrogen, oxygen, or sulfur, phenyl, a 3-7 membered saturated    or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur;-   each of R² and R³ is independently R′, —OR′, —SR′, —N(R′)₂,    —OC(O)R′, —SOR′, —SO₂R′, —SO₂N(R′)₂, —C(O)N(R′)₂, —NR′C(O)R′, or    —NR′SO₂R′;-   m is 0-3;-   Ring B is an optionally substituted group selected from phenyl or a    5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms    independently selected from nitrogen, oxygen, or sulfur;-   each of p and q is independently 0-4;-   each of Ring C and Ring D is independently an optionally substituted    5-membered monocyclic heteroaryl ring having 1-4 nitrogen atoms;-   each of R^(x), R^(y) and R^(z) is independently halogen, —OR′,    —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)₂, —NR′SO₂R′,    —NR′SO₂N(R′)₂, —NR′OR′, or an optionally substituted group selected    from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, phenyl, a    3-7 membered saturated or partially unsaturated carbocyclic ring, an    8-10 membered bicyclic saturated, partially unsaturated or aryl    ring, a 5-6 membered monocyclic heteroaryl ring having 1-4    heteroatoms independently selected from nitrogen, oxygen, or sulfur,    a 3-7 membered saturated or partially unsaturated heterocyclic ring    having 1-3 heteroatoms independently selected from nitrogen, oxygen,    or sulfur, a 7-10 membered bicyclic saturated or partially    unsaturated heterocyclic ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, or an 8-10 membered    bicyclic heteroaryl ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur;-   R⁴ is an optionally substituted 5-membered monocyclic heteroaryl    ring having 1-2 nitrogen atoms; and-   each R′ is independently hydrogen or an optionally substituted group    selected from C₁₋₆ aliphatic, phenyl, a 3-7 membered saturated or    partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur; or:    -   two R′ groups on the same nitrogen atom are optionally taken        together with the nitrogen atom to form an optionally        substituted 3-8 membered, saturated, partially unsaturated, or        aryl ring having 1-4 heteroatoms independently selected from        nitrogen, oxygen, or sulfur.        E2. The compound of example E1, wherein each of R² and R³ is        independently R′.        E3. The compound of any one of the preceding examples, wherein        one of R² and R³ is hydrogen and the other is not hydrogen.        E4. The compound of any one of the preceding examples, wherein        one of R² and R³ is hydrogen and the other is optionally        substituted C₁₋₂₀ aliphatic.        E5. The compound of any one of the preceding examples, wherein        one of R² and R³ is hydrogen and the other is —C(Me)₃ or        —C(Me)₂Ph.        E6. A compound of formula II:

wherein:

-   M is molybdenum or tungsten;-   R¹ is an optionally substituted group selected from C₁₋₂₀ aliphatic,    C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms independently selected    from nitrogen, oxygen, or sulfur, phenyl, a 3-7 membered saturated    or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur;-   R^(2′) and R^(3′) are taken together with their intervening metal    atoms to form an optionally substituted 3-8 membered saturated or    partially unsaturated ring having, in addition to the intervening    metal atom, 0-4 heteroatoms independently selected from nitrogen,    oxygen, or sulfur;-   m is 0-3;-   Ring B is an optionally substituted group selected from phenyl or a    5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms    independently selected from nitrogen, oxygen, or sulfur;-   each of p and q is independently 0-4;-   each of Ring C and Ring D is independently an optionally substituted    5-membered monocyclic heteroaryl ring having 1-4 nitrogen atoms;-   each of R^(x), R^(y) and R^(z) is independently halogen, —OR′,    —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)₂, —NR′SO₂R′,    —NR′SO₂N(R′)₂, —NR′OR′, or an optionally substituted group selected    from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, phenyl, a    3-7 membered saturated or partially unsaturated carbocyclic ring, an    8-10 membered bicyclic saturated, partially unsaturated or aryl    ring, a 5-6 membered monocyclic heteroaryl ring having 1-4    heteroatoms independently selected from nitrogen, oxygen, or sulfur,    a 3-7 membered saturated or partially unsaturated heterocyclic ring    having 1-3 heteroatoms independently selected from nitrogen, oxygen,    or sulfur, a 7-10 membered bicyclic saturated or partially    unsaturated heterocyclic ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, or an 8-10 membered    bicyclic heteroaryl ring having 1-5 heteroatoms independently    selected from nitrogen, oxygen, or sulfur;-   R⁴ is an optionally substituted 5-membered monocyclic heteroaryl    ring having 1-2 nitrogen atoms; and-   each R′ is independently hydrogen or an optionally substituted group    selected from C₁₋₆ aliphatic, phenyl, a 3-7 membered saturated or    partially unsaturated carbocyclic ring, an 8-10 membered bicyclic    saturated, partially unsaturated or aryl ring, a 5-6 membered    monocyclic heteroaryl ring having 1-4 heteroatoms independently    selected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated    or partially unsaturated heterocyclic ring having 1-3 heteroatoms    independently selected from nitrogen, oxygen, or sulfur, a 7-10    membered bicyclic saturated or partially unsaturated heterocyclic    ring having 1-5 heteroatoms independently selected from nitrogen,    oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring    having 1-5 heteroatoms independently selected from nitrogen, oxygen,    or sulfur; or:    -   two R′ groups on the same nitrogen atom are optionally taken        together with the nitrogen atom to form an optionally        substituted 3-8 membered, saturated, partially unsaturated, or        aryl ring having 1-4 heteroatoms independently selected from        nitrogen, oxygen, or sulfur.        E7. The compound of example E6, wherein R^(2′) and R^(3′) are        taken together with M to form an optionally substituted        3-membered ring.        E8. The compound of example E6, wherein R^(2′) and R^(3′) are        taken together with M to form an optionally substituted        4-membered ring.        E9. The compound of example E6, wherein the compound has the        structure of formula II-a:

E10. The compound of example E6, wherein R^(2′) and R^(3′) are takentogether with M to form an optionally substituted 5-membered ring.E11. The compound of any one of the preceding examples, wherein R¹ isoptionally substituted C₁₋₂₀ aliphatic.E12. The compound of any one of the preceding examples, wherein R¹ isoptionally substituted adamantyl.E13. The compound of any one of examples E1-E10, wherein R¹ isoptionally substituted phenyl.E14. The compound of any one of examples E1-E10, wherein R¹ is selectedfrom

E15. The compound of any one of the preceding examples, wherein R⁴ isbonded to M through a nitrogen atom.E16. The compound of any one of the preceding examples, wherein R⁴ isoptionally substituted pyrrolyl.E17. The compound of any one of the preceding examples, wherein R⁴ is2,5-disubstituted pyrrolyl.E18. The compound of any one of examples E1-E15, wherein R⁴ is

E19. The compound of example E18, wherein R⁴ is

E20. The compound of example E18, wherein R⁴ is

E21. The compound of any one of the preceding examples, wherein R¹ is

E22. The compound of any one of the preceding examples, wherein R¹ is

E23. The compound of any one of the preceding examples, wherein R¹ is

E24. A compound of formula III:

or its salt thereof.E25. The compound of any one of the preceding examples, wherein Ring Cis optionally substituted pyrrolyl, imidazolyl or pyrazolyl.E26. The compound of any one of examples E1-E24, wherein Ring C is

E27. The compound of example E26, wherein Ring C is

E28. The compound of example E27, wherein Ring C is

E29. The compound of any one of the preceding examples, wherein Ring Dis optionally substituted pyrrolyl, imidazolyl or pyrazolyl.E30. The compound of any one of examples E1-E28, wherein Ring D is

E31. The compound of example E30, wherein Ring D is

E32. The compound of example E31, wherein Ring D is

E33. The compound of any one of the preceding examples, wherein Ring Cand Ring D are the same.E34. The compound of any one of examples E1-E32, wherein Ring C and RingD are different.E35. The compound of any one of the preceding examples, wherein at leastone of Ring C and Ring D is optionally substituted pyrrolyl.E36. The compound of any one of examples E1-E24, wherein

has the structure of:

E37. The compound of example E36, wherein

has the structure of:

E38. The compound of any one of examples E1-E24, where p is 4.E39a. The compound of any one of examples E1-E28, wherein q is 4.E39b. The compound of any one of the preceding examples, wherein Ring Bis optionally substituted phenyl or

E40. The compound of any of the preceding examples, wherein Ring B is

E41. The compound of example E36, wherein

E42. The compound of example E41, wherein

E43. The compound of example E42, wherein

E44. The compound of example E42, wherein

E45. The compound of example E1, wherein the compound is selected from

E46. The compound of example E6, wherein the compound is

E47. A method comprising:

-   -   (a) providing a compound of formula I or II; and    -   (b) reacting a first unsaturated carbon-carbon bond and a second        unsaturated carbon-carbon bond to produce a product comprising        an unsaturated carbon-carbon bond.        E48. The method of example E47, wherein the compound is a        compound of any one of examples E1-E23 and E25-E46.        E49. The method of example E47 or E48, wherein one of the first        and the second unsaturated bonds is a carbon-carbon double bond.        E50. The method of example E47 or E48, wherein each of the first        and the second unsaturated bonds is a carbon-carbon double bond,        and the product comprises a carbon-carbon double bond.        E51. The method of example E47 or E48, wherein one of the first        and the second unsaturated bonds is a carbon-carbon triple bond.        E52. The method of any one of examples E47-E51, wherein the        product comprises an unsaturated carbon-carbon bond, wherein        said unsaturated carbon-carbon bond in the product comprises one        carbon atom from the first unsaturated bond and one carbon atom        from the second unsaturated bond.        E53. The method of any one of examples E47-E52, wherein the        product comprises a carbon-carbon double bond, and said        carbon-carbon double bond is formed with Z-selectivity.        E54. The method of any one of example E47-E53, wherein the        Z-selectivity is greater than about 60%.        E55. The method of example E54, wherein the Z-selectivity is        greater than about 70%.        E56. The method of example E55, wherein the Z-selectivity is        greater than about 80%.        E57. The method of example E56, wherein the Z-selectivity is        greater than about 90%.        E58. The method of example E57, wherein the Z-selectivity is        greater than about 95%.        E59. The method of any one of examples E47-E58, wherein the        compound comprising the first unsaturated carbon-carbon bond and        the compound comprising the second unsaturated carbon-carbon        bond are identical.        E60. The compound of example E24, wherein the compound has the        structure of:

or its salt thereof.E61. A method for preparing a metal complex, comprising the use of acompound of example E24.E62 The method of example E61, wherein the compound of example E24 is acompound of example E60.

Conditions

In some embodiments, a ligand is provided in a molar ratio of about10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, or 1:1 relative to themetal. In some embodiments, a ligand is provided in a molar ratio ofabout 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.4:1, 0.3:1, 0.2:1, or 0.1:1relative to the metal. In certain embodiments, a ligand is provided in amolar ratio of about 1:1 relative to the metal. One of skill in the artwill appreciate that the optimal molar ratio of ligand to metal willdepend on, inter alia, whether the ligand is mono- or polydentate. Insome embodiments, a ligand or ligand precursor having the structure offormula I is provided in a molar ratio of about 1:1 to Mo or W.

Suitable conditions for performing provided methods generally employ oneor more solvents. In certain embodiments, one or more organic solventsare used. Examples of such organic solvents include, but are not limitedto, hydrocarbons such as benzene, toluene, and pentane, halogenatedhydrocarbons such as dichloromethane, or polar aprotic solvents, such asethereal solvents including ether, tetrahydrofuran (THF), or dioxanes,or protic solvents, such as alcohols, or mixtures thereof. In certainembodiments, one or more solvents are deuterated.

In some embodiments, a single solvent is used. In certain embodiments, asolvent is benzene. In some embodiments, a solvent is toluene. Incertain embodiments, a solvent is ether. In some embodiments, a solventis a nitrile. In some embodiments, a solvent is acetonitrile.

In some embodiments, mixtures of two or more solvents are used, and insome cases may be preferred to a single solvent. In certain embodiments,the solvent mixture is a mixture of an ethereal solvent and ahydrocarbon. Exemplary such mixtures include, for instance, anether/benzene mixture. Solvent mixtures may be comprised of equalvolumes of each solvent or may contain one solvent in excess of theother solvent or solvents. In certain embodiments wherein a solventmixture is comprised of two solvents, the solvents may be present in aratio of about 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. Incertain embodiments wherein a solvent mixture comprises an etherealsolvent and a hydrocarbon, the solvents may be present in a ratio ofabout 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1,about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1 etherealsolvent:hydrocarbon. In certain embodiments, the solvent mixturecomprises a mixture of ether and benzene in a ratio of about 5:1. One ofskill in the art would appreciate that other solvent mixtures and/orratios are contemplated herein, that the selection of such other solventmixtures and/or ratios will depend on the solubility of species presentin the reaction (e.g., substrates, additives, etc.), and thatexperimentation required to optimized the solvent mixture and/or ratiowould be routine in the art and not undue.

Suitable conditions, in some embodiments, employ ambient temperatures.In some embodiments, a suitable temperature is about 15° C., about 20°C., about 25° C., or about 30° C. In some embodiments, a suitabletemperature is from about 15° C. to about 25° C. In certain embodiments,a suitable temperature is about 20° C., 21° C., 22° C., 23° C., 24° C.,or 25° C.

In certain embodiments, a provided method is performed at elevatedtemperature. In some embodiments, a suitable temperature is from about25° C. to about 110° C. In certain embodiments, a suitable temperatureis from about 40° C. to about 100° C., from about 50° C. to about 100°C., from about 60° C. to about 100° C., from about 70° C. to about 100°C., from about 80° C. to about 100° C., or from about 90° C. to about100° C. In some embodiments, a suitable temperature is about 80° C. Insome embodiments, a suitable temperature is about 30° C. In someembodiments, a suitable temperature is about 40° C. In some embodiments,a suitable temperature is about 50° C. In some embodiments, a suitabletemperature is about 60° C. In some embodiments, a suitable temperatureis about 70° C. In some embodiments, a suitable temperature is about 80°C. In some embodiments, a suitable temperature is about 90° C. In someembodiments, a suitable temperature is about 100° C. In someembodiments, a suitable temperature is about 110° C.

In certain embodiments, a provided method is performed at temperaturelower than ambient temperatures. In some embodiments, a suitabletemperature is from about −100° C. to about 10° C. In certainembodiments, a suitable temperature is from about −80° C. to about 0° C.In certain embodiments, a suitable temperature is from about −70° C. toabout 10° C. In certain embodiments, a suitable temperature is fromabout −60° C. to about 10° C. In certain embodiments, a suitabletemperature is from about −50° C. to about 10° C. In certainembodiments, a suitable temperature is from about −40° C. to about 10°C. In certain embodiments, a suitable temperature is or from about −30°C. to about 10° C. In some embodiments, a suitable temperature is below0° C. In some embodiments, a suitable temperature is about −100° C. Insome embodiments, a suitable temperature is about −90° C. In someembodiments, a suitable temperature is about −80° C. In someembodiments, a suitable temperature is about −70° C. In someembodiments, a suitable temperature is about −60° C. In someembodiments, a suitable temperature is about −50° C. In someembodiments, a suitable temperature is about −40° C. In someembodiments, a suitable temperature is about −30° C. In someembodiments, a suitable temperature is about −20° C. In someembodiments, a suitable temperature is about −10° C. In someembodiments, a suitable temperature is about 0° C. In some embodiments,a suitable temperature is about 10° C.

In some embodiments, a provided method is performed at differenttemperatures. In some embodiments, temperature changes in a providedmethod. In some embodiments, a provided method involves temperatureincrease from a lower suitable temperature to a higher suitabletemperature. In some embodiments, a provided method comprisestemperature increase from about −80° C., about −70° C., about −60° C.,about −50° C., about −40° C., about −30° C., about −20° C., about −10°C., and about 0° C. to about 0° C., about 10° C., about 20° C., ambienttemperature, about 22° C., about 25° C., about 30° C., about 40° C.,about 50° C., about 60° C., about 70° C., about 80° C., about 90° C.,about 100° C. and about 110° C. In some embodiments, a provided methodcomprises temperature increase from about −30° C. to 22° C. In someembodiments, a provided method comprises temperature decrease from ahigher suitable temperature to a lower suitable temperature. In someembodiments, a provided method comprises temperature increase from about110° C., about 100° C., about 90° C., about 80° C., about 70° C., about60° C., about 50° C., about 40° C., about 30° C., about 25° C., about22° C., ambient temperature, about 20° C., about 10° C., and about 0° C.to about 0° C., about −10° C., about −20° C., about −30° C., about −40°C., about −50° C., about −60° C., about −70° C., about −80° C., about−90° C., and about −100° C.

Suitable conditions typically involve reaction times of about 1 minuteto about one or more days. In some embodiments, the reaction time rangesfrom about 0.5 hour to about 20 hours. In some embodiments, the reactiontime ranges from about 0.5 hour to about 15 hours. In some embodiments,the reaction time ranges from about 1.0 hour to about 12 hours. In someembodiments, the reaction time ranges from about 1 hour to about 10hours. In some embodiments, the reaction time ranges from about 1 hourto about 8 hours. In some embodiments, the reaction time ranges fromabout 1 hour to about 6 hours. In some embodiments, the reaction timeranges from about 1 hour to about 4 hours. In some embodiments, thereaction time ranges from about 1 hour to about 2 hours. In someembodiments, the reaction time ranges from about 2 hours to about 8hours. In some embodiments, the reaction time ranges from about 2 hoursto about 4 hours. In some embodiments, the reaction time ranges fromabout 2 hours to about 3 hours. In certain embodiments, the reactiontime is about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 hours. In certainembodiments, the reaction time is about 1 hour. In certain embodiments,the reaction time is about 2 hours. In certain embodiments, the reactiontime is about 3 hours. In certain embodiments, the reaction time isabout 4 hours. In certain embodiments, the reaction time is about 5hours. In certain embodiments, the reaction time is about 6 hours. Insome embodiments, the reaction time is about 12 hours. In certainembodiments, the reaction time is less than about 1 hour. In certainembodiments, the reaction time is about 5, 10, 15, 20, 25, 30, 35, 40,45, 50, or 55 minutes. In some embodiments, the reaction time is about 5minutes. In some embodiments, the reaction time is about 10 minutes. Insome embodiments, the reaction time is about 15 minutes. In someembodiments, the reaction time is about 20 minutes. In some embodiments,the reaction time is about 25 minutes. In some embodiments, the reactiontime is about 30 minutes. In some embodiments, the reaction time isabout 35 minutes. In some embodiments, the reaction time is about 40minutes. In some embodiments, the reaction time is about 100 minutes. Insome embodiments, the reaction time is about 110 minutes. In someembodiments, the reaction time is about 200 minutes. In someembodiments, the reaction time is about 300 minutes. In someembodiments, the reaction time is about 400 minutes.

Some embodiments may provide the ability to selectively synthesize, viaa metathesis reaction, products having a Z or E configuration about adouble bond. In some embodiments, a method of the present inventionprovides the ability to synthesize compounds comprising a Z-olefin. Insome embodiments, such methods are useful when applied to a wide rangeof olefin substrates, including those having sterically small or largegroups adjacent the olefin. In some embodiments, the substrate olefinsare terminal olefins.

In some embodiments, the present invention provides a method forZ-selective metathesis reactions. In some embodiments, a provided methodproduces a double bond in a Z:E ratio greater than about 1:1, greaterthan about 2:1, greater than about 3:1, greater than about 4:1, greaterthan about 5:1, greater than about 6:1, greater than about 7:1, greaterthan about 8:1, greater than about 9:1, greater than about 95:5, greaterthan about 96:4, greater than about 97:3, greater than about 98:2, or,in some cases, greater than about 99:1, as determined using methodsdescribed herein (e.g., HPLC or NMR). In some cases, about 100% of thedouble bond produced in the metathesis reaction may have a Zconfiguration. The Z or cis selectivity may also be expressed as apercentage of product formed. In some cases, the product may be greaterthan about 50% Z, greater than about 60% Z, greater than about 70% Z,greater than about 80% Z, greater than about 90% Z, greater than about95% Z, greater than about 96% Z, greater than about 97% Z, greater thanabout 98% Z, greater than about 99% Z, or, in some cases, greater thanabout 99.5% Z.

In some embodiments, a provided compound isomerizes a product. In someembodiments, a provided compound isomerizes a Z product. In someembodiments, a provided compound isomerizes a Z product slower than theformation of the product. In some embodiments, a provided compoundisomerizes an E product. In some embodiments, a provided compoundisomerizes an E product slower than the formation of the product.

In some embodiments, a provided compound does not isomerize a product.In some embodiments, a provided compound does not isomerize a Z product.In some embodiments, a provided compound does not isomerize an Eproduct.

In some embodiments, a provided metal complex compound, e.g. a compoundof formula I or II, or an active catalyst formed from a providedcompound, is stable under metathesis conditions. In some embodiments, aprovided compound, or an active catalyst formed from a providedcompound, decomposes under metathesis conditions. In some embodiments, aprovided compound, or an active catalyst formed from a providedcompound, decomposes under metathesis conditions within about 1 hour. Insome embodiments, a provided compound, or an active catalyst formed froma provided compound, decomposes under metathesis conditions within about2 hours. In some embodiments, a provided compound, or an active catalystformed from a provided compound, decomposes under metathesis conditionswithin about 6 hours. In some embodiments, a provided compound, or anactive catalyst formed from a provided compound, decomposes undermetathesis conditions within about 12 hours. In some embodiments, aprovided compound, or an active catalyst formed from a providedcompound, decomposes under metathesis conditions within about 24 hours.In some embodiments, a provided compound, or an active catalyst formedfrom a provided compound, decomposes under metathesis conditions withinabout 48 hours. In some embodiments, a provided compound, or an activecatalyst formed from a provided compound, decomposes under metathesisconditions within about 96 hours.

In some embodiments, a provided compound, or an active catalyst formedfrom a provided compound, decomposes prior to isomerization of aproduct. In some embodiments, a provided compound, or an active catalystformed from a provided compound, partially decomposes prior toisomerization of a product. In some embodiments, a provided compound, oran active catalyst formed from a provided compound, decomposes prior toisomerization of a Z product. In some embodiments, a provided compound,or an active catalyst formed from a provided compound, partiallydecomposes prior to isomerization of a Z product. In some embodiments, aprovided compound, or an active catalyst formed from a providedcompound, decomposes prior to isomerization of an E product. In someembodiments, a provided compound, or an active catalyst formed from aprovided compound, partially decomposes prior to isomerization of an Eproduct.

In some embodiments, a metathesis reaction using a compound of thepresent invention produces a polymer wherein the polymer is >50%cis, >50% syndiotactic. In some embodiments, a metathesis reaction usinga compound of the present invention produces a polymer wherein thepolymer is >60% cis, >60% syndiotactic. In some embodiments, ametathesis reaction using a compound of the present invention produces apolymer wherein the polymer is >70% cis, >70% syndiotactic. In someembodiments, a metathesis reaction using a compound of the presentinvention produces a polymer wherein the polymer is 80% cis, >80%syndiotactic. In some embodiments, a metathesis reaction using acompound of the present invention produces a polymer wherein the polymeris >90% cis, 90% syndiotactic. In some embodiments, a metathesisreaction using a compound of the present invention produces a polymerwherein the polymer is >95% cis, 90% syndiotactic. In some embodiments,a metathesis reaction using a compound of the present invention producesa polymer wherein the polymer is >99% cis, 90% syndiotactic. In someembodiments, a metathesis reaction using a compound of the presentinvention produces a polymer wherein the polymer is >90% cis, >95%syndiotactic. In some embodiments, a metathesis reaction using acompound of the present invention produces a polymer wherein the polymeris >95% cis, >95% syndiotactic. In some embodiments, a metathesisreaction using a compound of the present invention produces a polymerwherein the polymer is >99% cis, >90% syndiotactic. In some embodiments,a metathesis reaction using a compound of the present invention producesa polymer wherein the polymer is >99% cis, >95% syndiotactic. In someembodiments, a metathesis reaction using a compound of the presentinvention produces a polymer wherein the polymer is >99% cis, >97%syndiotactic. In some embodiments, a metathesis reaction using acompound of the present invention produces a polymer wherein the polymeris >99% cis, >99% syndiotactic.

In some embodiments, a provided method requires an amount of a providedcompound (e.g., a metal complex having the structure of formula I or II)such that the loading is from about 0.01 mol % to about 20 mol % of theprovided compound relative to substrate (e.g., a first or second doublebond). In certain embodiments, a provided compound is used in an amountof between about 0.01 mol % to about 10 mol %. In certain embodiments, aprovided compound is used in an amount of between about 0.01 mol % toabout 6 mol %. In certain embodiments, a provided compound is used in anamount of between about 0.01 mol % to about 5 mol %. In certainembodiments, a provided compound is used in an amount of between about0.01 mol % to about 4 mol %. In certain embodiments, a provided compoundis used in an amount of between about 0.01 mol % to about 3 mol %. Incertain embodiments, a provided compound is used in an amount of betweenabout 0.01 mol % to about 1 mol %. In certain embodiments, a providedcompound is used in an amount of between about 0.01 mol % to about 0.5mol %. In certain embodiments, a provided compound is used in an amountof between about 0.01 mol % to about 0.2 mol %. In certain embodiments,a provided compound is used in an amount of about 0.05%, 0.1%, 0.2%,0.5%, 1%, 2%, 3 mol %, 4 mol %, 5 mol %, 6 mol %, 7 mol %, 8 mol %, 9mol %, or 10 mol %.

In some embodiments, a method of the present invention requires anamount of solvent such that the concentration of the reaction is betweenabout 0.01 M and about 1 M. In some embodiments, the concentration ofthe reaction is between about 0.01 M and about 0.5 M. In someembodiments, the concentration of the reaction is between about 0.01 Mand about 0.1 M. In some embodiments, the concentration of the reactionis between about 0.01 M and about 0.05 M. In some embodiments, theconcentration of the reaction is about 0.01 M. In some embodiments, theconcentration of the reaction is about 0.02 M. In some embodiments, theconcentration of the reaction is about 0.03 M. In some embodiments, theconcentration of the reaction is about 0.04 M. In some embodiments, theconcentration of the reaction is about 0.05 M. In some embodiments, theconcentration of the reaction is about 0.1 M. In some embodiments, theconcentration of the reaction is about 0.3 M.

In some embodiments, a method of the present invention is performed atambient pressure. In some embodiments, a method of the present inventionis performed at reduced pressure. In some embodiments, a method of thepresent invention is performed at a pressure of less than about 20 torr.In some embodiments, a method of the present invention is performed at apressure of less than about 15 torr. In some embodiments, a method ofthe present invention is performed at a pressure of less than about 10torr. In some embodiments, a method of the present invention isperformed at a pressure of about 9, 8, 7, 6, 5, 4, 3, 2, or 1 torr. Incertain embodiments, a method of the present invention is performed at apressure of about 7 torr. In certain embodiments, a method of thepresent invention is performed at a pressure of about 1 torr. In someembodiments, a method of the present invention is performed at increasepressure. In some embodiments, a method of the present invention isperformed at greater than about 1 atm. In some embodiments, a method ofthe present invention is performed at greater than about 2 atm. In someembodiments, a method of the present invention is performed at greaterthan about 3 atm. In some embodiments, a method of the present inventionis performed at greater than about 5 atm. In some embodiments, a methodof the present invention is performed at greater than about 10 atm. Insome embodiments, a method of the present invention is performed atabout 2 atm. In some embodiments, a method of the present invention isperformed at about 3 atm. In some embodiments, a method of the presentinvention is performed at about 5 atm. In some embodiments, a method ofthe present invention is performed at about 10 atm.

In some embodiments, a method of the present invention is performed atincreased pressure. In some embodiments, a method of the presentinvention is performed at greater than about 1 atm. In some embodiments,a method of the present invention is performed at greater than about 2atm. In some embodiments, a method of the present invention is performedat greater than about 3 atm. In some embodiments, a method of thepresent invention is performed at greater than about 5 atm. In someembodiments, a method of the present invention is performed at greaterthan about 10 atm. In some embodiments, a method of the presentinvention is performed at about 2 atm. In some embodiments, a method ofthe present invention is performed at about 3 atm. In some embodiments,a method of the present invention is performed at about 5 atm. In someembodiments, a method of the present invention is performed at about 10atm.

As mentioned above, provided compounds are useful for metathesisreactions. Exemplary such methods and reactions are described below.

It will be appreciated that, in certain embodiments, each variablerecited for the above method is as defined above and described inembodiments, herein, singly and in combination.

EXEMPLIFICATION

The present invention recognizes, among other things, that there is acontinuing demand for sterically demanding ligands for metathesiscatalysts. In some embodiments, the present invention provides newcompounds that can be used as ligand precursors to prepare metalcomplexes that promote highly efficient and Z-selective metathesisreactions. In some embodiments, the present invention provides new metalcomplexes that promote highly efficient and Z-selective metathesisreactions. In some embodiments, the present invention provides methodsfor preforming highly efficient and Z-selective metathesis reactions.Exemplary but non-limiting examples are depicted herein. In someembodiments, the present invention provides metal complexes that containO-2,6-(2,5-R₂Pyrrolyl)₂C₆H₃ (2,6-DiPyrrolylPhenoxide or ODPP^(R))ligands. In some embodiments, R=i-Pr or Ph.

2-Methoxy-1,3-diaminobenzene was prepared from2-bromo-1,3-dinitrobenzene as shown in equation 1. The pyrrolyl groupswere then constructed employing the desired γ-diketone in a Paal-Knorrcondensation followed by deprotection with BBr₃. Both DPP^(Ph)OH andDPP^(iPr)OH were purified employing column chromatography andrecrystallized from hexane (DPP^(iPr)OH) or isopropanol.

Addition of one equivalent of DPP^(Ph)OH or DPP^(iPr)OH toMo(NAd)(CHCMe₂Ph)(Pyr)₂, Mo(NAd)(CHCMe₂Ph)(Me₂Pyr)₂,Mo(NAr)(CHCMe₂Ph)(Pyr)₂ and Mo(NAr)(CHCMe₂Ph)(Me₂Pyr)₂ (Ad=1-adamantyl,Ar=2,6-i-Pr₂C₆H₃, Pyr=pyrrolide; Me₂Pyr=2,5-dimethylpyrrolide) producedMAP complexes 1a, 1b, 2a, 2b, 3a, and 3b (Hock, A. S.; Schrock, R. R.;Hoveyda, A. H. J. Am. Chem. Soc. 2006, 128, 16373).

1a; R″=Ad, R′=H, OR=ODPP^(Ph) 1b; R″=Ad, R′=H, OR=ODPP^(iPr) 2a; R″=Ad,R′=Me, OR=ODPP^(Ph) 2b; R″=Ar, R′=Me, OR=ODPP^(Ph) 3a; R″=Ar, R′=H,OR=ODPP^(Ph) 3b; R″=Ar, R′=H, OR=ODPP^(iPr)

The reaction to give 1a required heating the mixture for one hour at 80°C., whereas the reaction to give 1b was complete at 22° C. (˜20 mM)within four hours. For steric reasons, the reactions to give 2a and 2bwere slower than those that yielded 1a and 1b. It should be noted, forcomparison, that both Mo(NAd)(CHCMe₂Ph)(Pyr)(OHIPT)^(5a) andMo(NAr)(CHCMe₂Ph)(Pyr)(OHIPT)⁹ have been prepared (the latter in situ)from Mo(NR)(CHCMe₂Ph)(Pyr)₂ (R=Ad or Ar) and one equivalent of HIPTOH.Therefore, ODPP^(Ph) and ODPP^(iPr) appear to behave approximately likethe OHIPT ligand, at least in terms of the synthesis of MAP speciesthrough protonation of bispyrrolides.

The X-ray structure of Mo(NAr)(CHCMe₂Ph)(Me₂Pyr)(ODPP^(Ph)) (2b) isshown in FIG. 1. The dihedral angles between the phenyl ring inODPP^(Ph) and the pyrrolyl rings are 83.7(3)° (C41-C42-N3-C47) and68.7(3)° (C41-C46-N-4-C67). In the structure ofMo(NAr)(CHCMe₂Ph)(Pyr)(ODPP^(iPr)) (3b) (FIG. 2) the dihedral anglesbetween the phenyl ring in ODPP^(iPr) and the pyrrolyl rings are70.3(2)° (C21-C22-N1-C30) and 80.8(2)° (C21-C26-N2-C37). The Mo—O—Cangle is larger in 3b (167.42(9)^(°)) than in 2b (153.7(1)°), consistentwith the greater steric demand of the ODPP^(iPr) ligand system than theODPP^(Ph) ligand system. Other bond distances and angles in the twostructures can be found below.

The reaction between W(NAr)(CH-t-Bu)(Pyr)₂(dme) and one equivalent ofDPP^(Ph)OH led to W(NAr)(CH-t-Bu)(Pyr)(ODPP^(Ph)) (4a). The reaction wasperformed in a sonicator bath due to the limited solubility ofDPP^(Ph)OH in C₆H₆. Since DPP^(iPr)OH is more soluble in benzene thanDPP^(Ph)OH in benzene, sonication was not required for the synthesis ofW(NAr)(CH-t-Bu)(Pyr)(ODPP^(iPr)) (4b).

4a; OR=ODPP^(Ph) 4b; OR=ODPP^(iPr)

Compound 4a reacts readily with ethylene to yield a metallacyclobutanecomplex, W(NAr)(C₃H₆)(Pyr)(ODPP^(Ph)) (5). Without the intention to belimited by theory, according to proton and carbon NMR data 5 has a TBPgeometry. However, the structure of 5 in the solid state (FIG. 3) iscloser to a square pyramidal structure, according to the τ value (0.26),which for a SP is 0 and for a perfect TBP is 1 (Addison, A. W.; Rao, T.J.; Reedijk, J.; van Rijn, J.; Verschoor, G. C. J. Chem. Soc., DaltonTrans. 1984, 1349). The metallacyclobutane carbon atom in approximatelythe apical position (W-C1=2.035(2)Å) is closer to the metal than is thecarbon atom in the basal position (W-C2=2.083(2)Å) by a statisticallysignificant amount (FIG. 4). The C_(α)-C_(β) bond lengths (1.590(3) and1.603(3)) are (barely) statistically different and in the directionthat, without the intention to be limited by theory, implies an ethylenethat contains C2 and C3 is approaching or leaving the CNO face ofW(NAr)(CH₂)(Pyr)(ODPP^(Ph)) approximately trans to the pyrrolide (FIG.4). The W-C(2) distance is 2.370(2), which is 0.1-0.2 Å longer than atypical W-C single bond. Since the structure of 5 is different from asquare pyramidal complex (SP in FIG. 5) in which the imido group is inthe apical position and the metallacyclic ring in basal positions,another type that has been observed in the solid state and in solution(Yuan, J.; Townsend, E. M.; Schrock, R. R.; Goldman, A. S.; Müller, P.;Takase, M. Adv. Syn. Catal. 2011, 353, 1985), we will call the structureof 5 an SP′ metallacyclobutane structure.

Selected distances and angles (averages) in the structures of fiveunsubstituted tungstacyclobutane TBP complexes (Flook, M. M.; Jiang, A.J.; Schrock, R. R.; Müller, P.; Hoveyda, A. H. J. Am. Chem. Soc. 2009,131, 7962; Marinescu, S.C.; Schrock, R. R.; Müller, P.; Takase, M. K.;Hoveyda, A. H. Organometallics 2011, 30, 1780; and Jiang, A. J.;Simpson, J. H.; Müller, P.; Schrock, R. R. J. Am. Chem. Soc. 2009, 131,7770), which have τ values from 0.47 to 0.68, including both complexesin the asymmetric unit of the structure ofW(NAr)(C₃H₆)(MePyr)(OBr₂Bitet) (Jiang, A. J.; Simpson, J. H.; Müller,P.; Schrock, R. R. J. Am. Chem. Soc. 2009, 131, 7770), and the one βsubstituted SP structure (W(NAr)[CH₂CH(Ph)CH₂](Pyr)(OHIPTNMe₂) (Yuan,J.; Townsend, E. M.; Schrock, R. R.; Goldman, A. S.; Müller, P.; Takase,M. Adv. Syn. Catal. 2011, 353, 1985), in which τ=0.06) are shown in FIG.5. The TBP and SP′ structures are closer to the transition state forolefin loss from the metallacyclobutane ring than is the SP structure,and the SP′ structure is the closest. Without the intention to belimited by theory, τ values for the TBP metallacyclobutane complexes areunlikely to approach 1 as a consequence of the constraints inherent in acomplex that contains a metallacylobutane ring in the equatorialposition; the maximum is ˜0.68.

While not wishing to be limited by theory, the findings here areconsistent with those concerning metallacyclobutanes made from MAPalkylidenes ((a) Solans-Monfort, X.; Clot, E.; Coperet, C.; Eisenstein,O. J. Am. Chem. Soc. 2005, 127, 14015; (b) Poater, A.; Solans-Monfort,X.; Clot, E.; Coperet, C.; Eisenstein, O. J. Am. Chem. Soc. 2007, 129,8207; (c) Solans-Monfort, X.; Copéret, C.; Eisenstein, O. J. Am. Chem.Soc. 2010, 132, 7750; (d) Solans-Monfort, X.; Copéret, C.; Eisenstein,O. Organometallics 2012, 31, 6812). The olefin approaches the more“open” CNO (imido/alkylidene/OR) face “trans” to the pyrrolide to yielda square pyramidal metallacyclobutane in which the ring spans apical andbasal sites, a structure that is essentially that found here. Thestructure becomes a TBP when the O-M-N_(imido) angle opens to ˜180° andthe pyrrolide moves into an equatorial position where the N2-M-C3 andN2-M-C1 angles are equal. A continuation of the movement of N2, N1, andO leads to another SP′ structure in which the metallacyclobutane againspans apical (now C3) and basal (now C1) sites and the ethylene that isleaving the coordination sphere contains C1 and C2. Both experimentallyand theoretically the barrier for interconversion of TBP and SP forms ingeneral is relatively low (For relatively recent studies see (a) Moberg,C. Angew. Chem. Int. Ed. 2011, 50, 10290. (b) Couzijn, E. P. A.;Slootweg, J. C.; Ehlers, A. W.; Lammertsma, K. J. Am. Chem. Soc. 2010,132, 18127). The energy barrier for interconversion of TBP and SP′metallacyclobutane structures seems likely to be significantly evenlower since minimal movement of the imido and aryloxide ligands isrequired.

Regarding why the structure of 5 is SP′ instead of TBP, without theintention to be limited by theory, we reason that the energy differencebetween the two could be so low that intramolecular steric forces and/orpacking forces in the crystal tip the balance in favor of SP′. In someembodiments, evidence consists of a loss of mirror symmetry in themetallacylobutane ring at low temperatures.

The ROMP polymerization of 50 equivalents of 5,6-dicarbomethoxynorbornadiene was chosen as an initial measure of thestereoselectivity of the six MAP catalysts described earlier. Althoughthe rates of the polymerizations varied in terms of steric hindrancearound the metal, all polymers were found to have a >99% cis,syndiotactic structure.

Compounds 4a and 4b are highly active for the homocoupling of 1-octene(Table 1). For comparison, W(NAr)(C₃H₆)(pyr)(OHIPT) (6) was tested underidentical conditions. Both compounds 4a and 4b provide a significantlyfaster rate than 6. Catalyst 4a provided 62% conversion and >95%Z-selectivity in 10 minutes. Catalyst 4b provided 83% conversion over400 minutes with >95% Z-selectivity.

TABLE 1 Homocoupling of 1-octene with 4a and 4b.a Catalyst t(min) % Conv% Z 4a 10 62 >95 4a 40 72 90 4a 110 88 84 4a 400 >95 62 4b 10 24 — 4b 4036 — 4b 110 59 >95 4b 400 83 94 6 10 5 — 6 40 16 — 6 110 46 >95 6 40093 >95 aConditions: 25° C., 4 mol % catalyst loading, 0.3M in C₆H₆.

General Procedures.

All manipulations were conducted under a nitrogen atmosphere in a VacuumAtmospheres drybox or using Schlenk techniques unless otherwisespecified. All glassware was oven-dried prior to use. Ether, pentane,toluene, and benzene were degassed with dinitrogen and passed throughactivated alumina columns under nitrogen. All dried and deoxygenatedsolvents were stored over molecular sieves in a nitrogen-filledglovebox. NMR spectra were recorded on a Bruker or Varian 300 MHz, 400MHz, 500 MHz or 600 MHz spectrometer at room temperature unlessotherwise specified. Chemical shifts for ¹H spectra were referenced tothe residual resonances of the deuterated solvent and are reported asparts per million relative to tetramethylsilane.2-Bromo-1,3-dinitrobenzene (Sienkowska, M.; Benin, V.; Kaszynski, P.Tetrahedron 2000, 56, 165), 2,7-dimethyloctane-3,6-dione (Ito, Y.;Konoike, T.; Saegusa, T. J. Am. Chem. Soc., 1975, 97, 2912),Mo(NAd)(CHCMe₂Ph)(Pyr)₂ (Hock, A. S.; Schrock, R. R.; Hoveyda, A. H. J.Am. Chem. Soc. 2006, 128, 16373), W(NAr)(CH-t-Bu)(Pyr)₂(dme)(Kreickmann, T.; Arndt, S.; Schrock, R. R.; Mueller, P. Organometallics2007, 26, 5702) and DCMNBD (Tabor, D.C.; White, F. H.; Collier, L. W.;Evans, S. A. J. Org. Chem. 1983, 48, 1638) were prepared according tothe literature. Analytical data were obtained from the CENTC ElementalAnalysis Facility at the University of Rochester, funded by NSFCHE-0650456, or by Midwest Microlabs, Indianapolis, Ind.

2-methoxy-1,3-dinitrobenzene

An argon filled Schlenk flask was charged with 25.77 g (104 mmol) of2-bromo-1,3-dinitrobenzene, 150 mL of absolute methanol was added andthe reaction mixture was chilled in an ice bath. 2.4 g (104 mmol) of Nawas added, and the resulting reaction mixture was purged with argonuntil all Na was dissolved and stirred at RT over night. The solvent wasremoved, the residue was re-suspended in acetone and filtered throughCelite to remove NaBr. The solvent was removed, and the crude productwas recrystallized from iPrOH. Yield: 19.8 g (90%). ¹H NMR (CDCl₃): δ8.05 (d, J_(HH)=8.2 Hz, 2H, Ar), 7.38 (t, J_(HH)=8.2 Hz, 1H, Ar), 4.07(s, 3H, OCH₃) ppm.

2-methoxybenzene-1,3-diamine

A 2 L round bottomed flask was charged with 23 g (116 mmol)2-methoxy-1,3-dinitrobenzene and 261 g (1.16 mol) tin chloridedihydrate. 160 mL EtOH was added, and the resulting suspension wasstirred at 70° C. for 90 min. In the beginning, the reaction is veryexothermic be careful! The solvent was removed and the reaction mixturewas diluted with H₂O and slowly added to about 500 mL of a 10 M NaOHsolution. The suspension was cooled down to RT and extracted three timeswith EtOAc. The combined organic layers were dried over MgSO₄, filteredand the solvent was removed under reduced pressure. The product wasobtained as red oil and used without further purification.

Yield: 13 g (81%). ¹H NMR (CDCl₃): δ 6.73 (t, J_(HH)=7.8 Hz, 1H, Ar),6.18 (d, J_(HH)=7.8 Hz, 2H, Ar), 3.77 (s, 3H, OCH₃), 3.75 (bs, 4H, NH₂)ppm.

1,1′-(2-methoxy-1,3-phenylene)bis(2,5-diisopropylpyrrolyl)

A mixture of 2-methoxybenzene-1,3-diamine (8.5 g, 61.5 mmol),2,7-dimethyloctane-3,6-dione (23 g, 135 mmol), p-toluenesulfonic acidmonohydrate (40 mg, 0.21 mmol) and 120 mL toluene was refluxed in aDean-Stark apparatus for 24 h. The solution was filtered through silicagel, and the solvent was removed under reduced pressure. The pureproduct was obtained after column chromatography and (LM: toluene)recrystallization from iPrOH. Yield: 13.5 g (54%). ¹H NMR (CDCl₃): δ7.31(d, J_(HH)=7.7 Hz, 2H, Ar), 7.18 (t, J_(HH)=7.7 Hz, 1H, Ar), 5.99 (s,4H, Pyr), 3.08 (s, 3H, OCH₃), 2.61 (sep, J_(HH)=6.6 Hz, 4H, CHMe₂), 1.10(t, J_(HH)=6.6 Hz, 24H, CH(CH₃)₂) ppm.

1,1′-(2-methoxy-1,3-phenylene)bis(2,5-diphenylpyrrolyl)

The reaction was performed in the same manner as1,1′-(2-methoxy-1,3-phenylene)bis(2,5-diisopropylpyrrolyl). The pureproduct was obtained after column chromatography and (LM: toluene)recrystallization from iPrOH/acetone. Yield: 4.8 g (61%). ¹H NMR(CDCl₃): δ 7.18 (m, 12H, Ph), 7.10 (d, J_(HH)=7.8 Hz, 2H, Ar), 7.00 (m,8H, Ph), 6.88 (t, J_(HH)=7.8 Hz, 1H, Ar), 6.40 (s, 4H, Pyr), 2.45 (s,3H, OCH₃) ppm.

2,6-bis(2,5-diisopropylpyrrolyl)phenol (DPP^(iPr)OH)

In a dry box a 250 mL Schlenk flask was charged with 13.1 g (32 mmol)1,1′-(2-methoxy-1,3-phenylene)bis(2,5-diisopropylpyrrolyl) and 150 mLCH₂Cl₂. 18.3 mL (193 mmol) BBr₃ was added and the resulting solution wasstirred for 24 h at 55° C., chilled with and ice bath and quenched with100 mL H₂O. The aqueous solution was extracted three times with Et₂O.The combined organic layers were dried over MgSO₄, filtered and thesolvent was removed under reduced pressure. The pure produced wasobtained after column chromatography (LM: toluene) and recrystallizationfrom hexane. Yield: 8.3 g (66%). ¹H NMR (CDCl₃): δ 7.30 (d, J_(HH)=7.8Hz, 2H, Ar), 7.09 (t, J_(HH)=7.8 Hz, 1H, Ar), 6.04 (s, 4H, Pyr), 5.26(s, 1H, OH), 2.57 (sep, J_(HH)=6.8 Hz, 4H, CH(CH₃)₂), 1.11 (d,J_(HH)=6.8 Hz, 12H, CH(CH₃)₂), 1.04 (d, J_(HH)=6.8 Hz, 12H, CH(CH₃)₂)ppm. Anal. Calc. (%) for C₂₆H₃₆N₂O: C, 79.55; H, 9.24; N, 7.14. Found:C, 79.49; H, 9.27; N, 7.11.

2,6-bis(2,5-diphenylpyrrolyl)phenol (DPP^(Ph)OH)

The reaction was performed in the same manner as DPP^(iPr)OH. The pureproduct was obtained after column chromatography (LM: toluene) andrecrystallization from iPrOH. Yield: 887 mg (46%). ¹H NMR (CDCl₃): δ7.15 (m, 12H, Ph), 7.08 (d, J_(HH)=7.8 Hz, 2H, Ar), 6.96 (m, 8H, Ph),6.75 (t, J_(HH)=7.8 Hz, 1H, Ar), 6.40 (s, 4H, Pyr), 4.85 (s, 3H, OH)ppm. Anal. Calc. (%) for C₃₈H₂₈N₂O: C, 86.34; H, 5.34; N, 5.30. Found:C, 85.99; H, 5.50; N, 5.28.

Mo(NAd)(CHCMe₂Ph)(Pyr)(ODPP^(Ph)) (1a)

In a J-Young tube Mo(NAd)(CHCMe₂Ph)(Pyr)₂ (100 mg, 0.2 mmol) andDPP^(Ph)OH (104 mg, 0.2 mmol) was combined and 2 mL C₆D₆ was added. Theresulting solution was heated at 80° C. for 60 min, and the completenessof the reaction was confirmed by ¹H-NMR spectroscopy. The solvent wasremoved, and the residue was extracted with toluene, filtered throughCelite and covered with a layer of pentane. After 18 h at −30° C. ayellow powder was isolated: Yield: 113 mg (59%). ¹H NMR (C₆D₆): δ 12.29(s, 1H, Mo=CH, JCH=121.4 Hz), 7.34 (m, 2H, Ar), 7.24-6.96 (m, 25H, Ar),6.74 (m, 2H, Ar), 6.65 (m, 2H, Ar), 6.56 (m, 4H, Ar), 6.11 (m, 1H, Ar),1.78 (s, 3H, Mo=CHCMe₂Ph), 1.73 (m, 8H, NAd), 1.50 (s, 3H, Mo=CHCMe₂Ph),1.33 (m, 7H, NAd) ppm.

¹³C NMR(C₆D₆): δ 283.6 (Mo=C), 158.5, 148.9, 138.4, 138.0, 133.6, 133.5,133.0, 131.8, 131.6, 128.8, 128.7, 128.5, 128.2, 128.1, 126.9, 126.6,126.4, 120.4, 112.2, 111.1, 110.4, 77.6, 52.3, 43.7, 35.7, 32.5, 31.1,29.8 ppm. Anal. Calc. (%) for C₆₂H₅₈MoN₄O: C, 76.68; H, 6.02; N, 5.77.Found: C, 76.47; H, 6.31; N, 5.58.

Mo(NAd)(CHCMe₂Ph)(Pyr)(ODPP^(iPr)) (1b)

In a J-Young tube Mo(NAd)(CHCMe₂Ph)(Pyr)₂ (100 mg, 0.2 mmol) andDPP^(iPr)OH (78.5 mg, 0.2 mmol) was combined and 2 mL C₆D₆ was added.The resulting solution was stored at RT for 4 h. The completeness of thereaction was confirmed by ¹H-NMR spectroscopy. The solvent was removed,and the residue was extracted with toluene, filtered through Celite andcovered with a layer of pentane. After 18 h at −30° C. a yellow solidwas isolated: Yield: 123 mg (74%). ¹H NMR (C₆D₆): δ 12.32 (s, 1H, Mo=CH,JCH=122.1 Hz), 7.43 (m, 2H, Ar), 7.27-7.20 (m, 5H, Ar), 7.12 (m, 1H,Ar), 6.98 (m, 4H, Ar), 6.62 (t, 2H, NC2H4), 6.55 (t, 2H, NC2H4), 6.22(d, 2H, iPr₂pyrr), 6.15 (d, 2H, iPr₂pyrr), 2.84 (m, 2H, CH(CH₃)₂), 2.71(m, 2H, CH(CH₃)₂), 1.91 (m, 9H, NAd), 1.80 (s, 3H, Mo=CHCMe₂Ph), 1.67(s, 3H, Mo=CHCMe₂Ph), 1.49 (m, 6H, NAd), 1.16 (m, 12H, CH(CH₃)₂), 1.03(d, 6H, CH(CH₃)₂), 0.99 (d, 6H, CH(CH₃)₂) ppm. ¹³C NMR(C₆D₆): δ 290.2(Mo=C), 157.7, 149.4, 140.3, 139.7, 133.3, 132.7, 130.7, 128.5, 127.0,126.4, 120.7, 77.4, 52.3, 44.1, 35.9, 32.4, 32.2, 29.9, 26.7, 26.4,23.6, 23.2, 23.0, 22.3 ppm. Anal. Calc. (%) for C₅₀H₆₆MoN₄O: C, 71.92;H, 7.97; N, 6.71. Found: C, 71.92; H, 7.94; N, 6.68.

Mo(NAd)(CHCMe₂Ph)(Me₂Pyr)(ODPP^(Ph)) (2a)

The reaction was performed as reported for 1a, but the reaction time was4 h at 80° C. Yield: 92 mg (52%). ¹H NMR (C₆D₆): δ 12.06 (s, 1H, Mo=CH,JCH=121.7 Hz), 7.26 (m, 6H, Ar), 7.22-7.08 (m, 19H, Ar), 6.87 (d, 2H,Ar), 6.60 (s, 4H, Pyrr), 6.31 (bs, 2H, pyrr), 6.23 (t, 1H, Ar), 2.11(bs, 6H, Me₂Pyrr), 2.04 (s, 3H, Mo=CHCMe₂Ph), 1.98-183 (m, 9H, NAd),1.52 (s, 3H, Mo=CHCMe₂Ph), 1.43 (m, 6H, NAd) ppm. ¹³C NMR (C₆D₆): δ289.8(Mo=C), 158.8, 149.0, 137.3, 137.2, 133.6, 133.5, 132.0, 131.6, 128.7,128.6, 128.3, 128.2, 126.9, 126.6, 126.5, 126.4, 126.2, 120.3, 112.2,111.3, 77.9, 52.7, 44.0, 35.8, 34.0, 31.9, 29.9 ppm. Anal. Calc. (%) forC₆₄H₆₂MoN₄O: C, 76.93; H, 6.25; N, 5.61. Found: C, 77.29, H, 6.30; N,5.53.

Mo(NAr)(CHCMe₂Ph)(Me₂Pyr)(ODPP^(Ph)) (2b)

The reaction was performed as reported for 1a, but the reaction time was7d at 80° C. Yield: 115 mg (63%). ¹H NMR (C₆D₆): δ 12.48 (s, 1H, Mo=CH,JCH=122.1 Hz), 7.30-6.91 (m, 28H, Ar), 6.69 (d, 2H, Ar), 6.61 (d, 2H,pyrr), 6.54 (d, 2H, pyrr), 6.16 (bs, 1H, pyrr), 6.08 (t, 1H, Ar), 5.90(bs, 1H, pyrr), 3.61 (m, 1H, CH(CH₃)₂), 2.96 (m, 1H, CH(CH₃)₂), 1.85 (s,6H, Me₂Pyrr), 1.80 (s, 3H, Mo=CHCMe₂Ph), 1.48 (s, 3H, Mo=CHCMe₂Ph), 1.06(d, 6H, CH(CH₃)₂) 0.95 (m, 6H, CH(CH₃)₂) ppm. ¹³C NMR (C₆D₆): δ 296.8(Mo=C), 158.8, 153.5, 151.3, 147.3, 146.2, 133.4, 133.3, 132.4, 131.8,128.7, 128.6, 127.9, 127.7, 126.3, 126.2, 126.1, 123.6, 122.9, 120.5,113.3, 112.0, 109.7, 109.5, 56.5, 33.0, 30.1, 29.2, 27.1, 25.2, 24.8,23.4, 22.5, 18.0, 15.5, 14.0 ppm. Anal. Calc. (%) for C₆₆H₆₄MoN₄O: C,77.32; H, 6.29; N, 5.46. Found: C, 77.25; H, 6.45; N, 5.25.

Mo(NAr)(CHCMe₂Ph)(Pyr)(ODPP^(Ph)) (3a)

The reaction was performed as reported for 1a. Yield: 128 mg (69%). ¹HNMR (C₆D₆): δ 12.32 (s, 1H, Mo=CH, JCH=121.5 Hz), 7.39-6.93 (m, 27H,Ar), 6.75 (d, 2H, Ar), 6.55 (d, 2H, pyrr), 6.48 (d, 2H, pyrr), 6.28 (m,4H, pyrr), 6.11 (t, 1H, Ar), 3.32 (m, 2H, CH(CH₃)₂), 1.60 (s, 3H,Mo=CHCMe₂Ph), 1.35 (s, 3H, Mo=CHCMe₂Ph), 1.67 (d, 6H, CH(CH₃)₂), 1.03(d, 6H, CH(CH₃)₂) ppm. ¹³C NMR (C₆D₆): δ 294.6 (Mo=C), 158.1, 154.2,147.3, 147.1, 137.9, 137.8, 134.1, 133.4, 132.8, 131.9, 131.6, 129.0,128.6, 128.4, 128.3, 127.5, 126.7, 126.6, 126.5, 126.3, 123.1, 120.7,112.4, 12.0, 110.2, 56.8, 31.0, 30.2, 28.9, 24.5, 23.4 ppm. Anal. Calc.(%) for C₆₄H₆₂MoN₄O: C, 76.93; H, 6.25; N, 5.61. Found: C, 7.33; H,6.06; N, 5.54.

Mo(NAr)(CHCMe₂Ph)(Pyr)(ODPP^(iPr)) (3b)

The reaction was performed as reported for 1b. Yield: 116 mg (72%). ¹HNMR (C₆D₆): δ 13.01 (s, 1H, Mo=CH, JCH=122.9 Hz), 7.41 (m, 2H, Ar), 7.27(m, 2H, Ar), 7.21 (m, 2H, Ar), 7.11 (m, 1H, Ar), 7.02-6.96 (m, 4H, Ar),6.54 (t, 2H, NC2H4), 6.36 (t, 2H, NC2H4), 6.24 (m, 4H, iPr₂pyrr), 3.52(m, 2H, CH(CH₃)₂), 2.79 (m, 2H, CH(CH₃)₂), 2.73 (m, 2H, CH(CH₃)₂), 1.80(s, 3H, Mo=CHCMe₂Ph), 1.65 ((s, 3H, Mo=CHCMe₂Ph), 1.29 (m, 12H,CH(CH₃)₂), 1.10 (m, 12H, CH(CH₃)₂), 1.00 (m, 12H, CH(CH₃)₂) ppm. ¹³C NMR(C₆D₆): δ 298.5 (Mo=C), 157.4, 153.7, 147.9, 140.3, 139.9, 133.1, 131.3,131.2, 128.7, 127.7, 126.7, 126.6, 123.5, 121.0, 110.4, 104.4, 103.8,56.1, 31.1, 30.9, 25.8, 26.8, 26.3, 24.7, 24.4, 23.8, 23.2, 22.7, 22.1ppm. Anal. Calc. (%) for C₅₂H₆₈MoN₄O: C, 72.53; H, 7.96; N, 6.51. Found:C, 72.34; H, 7.95; N, 6.55.

W(NAr)(CH-t-Bu)(pyr)(ODPP^(Ph)) (4a)

A vessel containing a suspension of W(NAr)(CH-t-Bu)(pyr)₂(dme) (47.6 mg,0.0731 mmol) and 2,6-bis(2,5-diphenyl-N-pyrrolyl)phenol (38.6 mg, 0.0731mmol) in C₆H₆ was placed in a sonicator bath for 48 hours. All volatileswere removed in vacuo and the residue was extracted with pentane (5 mL)to provide the crude product. Recrystallization from toluene and pentaneyielded the product as a yellow-orange crystalline solid (46.1 mg, 62%yield). ¹H NMR (500 MHz, C₆D₆, 25° C.) δ 9.17 (br s, 1H, W=CH), 7.27 (m,4H, Ar), 7.07-6.95 (m, 15H, Ar), 6.87 (m, 4H, Ar), 6.67 (d, J=8.0 Hz,2H, Ar), 6.51-6.45 (m, 6H, Ar), 6.28 (m, 2H, Ar), 6.06 (t, J=8.0 Hz, 1H,Ar) δ 3.30 (sept, J=6.8 Hz, 2H, CH(CH₃)₂), 1.25 (d, J=6.8 Hz, 6H,CH(CH₃)₂), 1.00 (d, J=6.8 Hz, 6H, CH(CH₃)₂), 0.94 (s, 9H, ^(t)Bu).¹³C{¹H} NMR (125 MHz, C₆D₆, 25° C.) δ 264.92 (W=CHR), 157.38, 152.36,145.70, 137.74, 137.58, 135.24, 134.00, 133.22, 131.86, 131.65, 129.06,128.81, 128.60, 128.55, 128.45, 128.35, 127.45, 126.78, 126.46, 122.74,121.71, 112.75, 112.04, 111.49, 48.44, 32.60, 28.57, 24.45, 23.31. Anal.Calc. (%) for C₅₉H₅₈N₄OW: C, 69.27; H, 5.71; N, 5.48. Found: C, 69.18;H, 5.78; N, 5.37.

W(NAr)(CH-t-Bu)(pyr)(ODPP^(iPr)) (4b)

A vessel containing a solution of W(NAr)(CH-t-Bu)(pyr)₂(dme) (48.6 mg,0.0746 mmol) and 2,6-bis(2,5-diisopropyl-N-pyrrolyl)phenol (29.3 mg,0.0746 mmol) in C₆H₆ was heated at 60° C. for 16 hours. All volatileswere removed in vacuo and the residue was triturated with cold pentane(5 mL) to provide the crude product. Recrystallization from pentaneyielded the product as a yellow-orange crystalline solid (24.9 mg, 38%yield). ¹H NMR (500 MHz, C₆D₆, 25° C.) δ 10.02 (br s, 1H, W=CH), 7.06(m, 2H, Ar), 6.98 (m, 1H, Ar), 6.91 (m, 2H, Ar), 6.78 (m, 2H, Ar), 6.54(t, J=7.9 Hz, 1H, Ar), 6.36 (m, 2H, Ar), 6.17 (m, 4H, Ar), 3.58 (br s,2H, N(Ar)CH(CH₃)₂), 2.72-2.55 (m, 4H, ODPP CH(CH₃)₂), 1.33 (d, J=6.8 Hz,6H, CH(CH₃)₂), 1.25-1.17 (m, 15H, CH(CH₃)₂ and ^(t)Bu), 1.09 (d, J=6.8Hz, 6H, CH(CH₃)₂), 1.01 (d, J=6.5 Hz, 6H, CH(CH₃)₂), 0.93 (m, 12H,CH(CH₃)₂).

¹³C{¹H} NMR (125 MHz, C₆D₆, 25° C.) δ 268.61 (W=CHR), 157.34, 152.13,140.35, 139.75, 135.41, 131.44, 131.17, 126.31, 123.11, 122.01, 111.77,104.58, 104.41, 103.91, 47.17, 33.03, 28.25, 26.83, 26.26, 24.71, 24.22,23.80, 23.35, 22.71, 21.96. Anal. Calc. (%) for C₄₇H₆₆N₄OW: C, 63.65; H,7.50; N, 6.32. Found: C, 63.29; H, 7.38; N, 6.13.

W(NAr)(C₃H₆)(pyr)(ODPP^(Ph)) (5)

A solution of W(NAr)(CH-t-Bu)(pyr)(ODPP^(Ph)) in C₆D₆ was subjected tothree freeze-pump-thaw cycles and treated with ethylene (1 atm). After16 hours, the solution was lyophilized to quantitatively afford theproduct as a light yellow solid. ¹H NMR (500 MHz, C₆D₆, 25° C.) δ7.43-6.47 (m, 31H, Ar), 6.22 (t, J=7.9 Hz, 1H, Ar), 5.82 (m, 2H, Ar),4.46 (m, ¹J_(CH)=160 Hz, 2H, α-CH₂), 3.87 (sept, J=6.5 Hz, 2H,CH(CH₃)₂), 3.49 (m, ¹J_(CH)=150 Hz, 2H, α-CH₂), 1.13 (m, 12H, CH(CH₃)₂),−0.78 (m, ¹J_(CH)=155 Hz, 1H, β-CH₂), −1.38 (m, ¹J_(CH)=155 Hz, 1H,β-CH₂). ¹J_(CH) values were obtained by preparing a sample with ¹³Clabeled ethylene. ¹³C {¹H} NMR (125 MHz, C₆D₆, 25° C.) δ 157.50, 149.03,146.99, 137.90, 133.33, 131.89, 130.54, 129.33, 128.81, 128.62, 128.57,128.45, 126.83, 126.28, 125.70, 123.00, 118.59, 111.87, 109.49, 99.99,28.33, 24.66, 21.45 (C_(α)), −4.24 (C_(β)). Anal. Calc. (%) forC₅₇H₅₄N₄OW: C, 68.81; H, 5.47; N, 5.63. Found: C, 68.44; H, 5.35; N,5.18.

ROMP of DCMNBD

For a standard ROMP procedure, 100 mg (0.48 mmol) DCMNBD was dissolvedin about 1 ml toluene and added to a solution 2% of the isolatedcatalyst dissolved in about 1 ml toluene. After the reaction wascompleted (checked by ¹H-NMR) the polymer was isolated by drop wiseadding the reaction mixture into a stirred MeOH solution. After 1 h thepolymer was filtered off, washed with MeOH and dried in vacuo. Thepurity and tacticity of the compound was proven by ¹H and ¹³C NMRspectroscopy.

Homocoupling of 1-Octene

The procedure was adapted from Jiang et al (Jiang, A. J.; Zhao, Y.;Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 16630).1-octene (10 μL, 0.064 mmol) was added via syringe to a solution of anolefin metathesis catalyst (2.5 μmol) in benzene (200 μL). An internalstandard is also added to the reaction mixture (trimethoxybenzene ormesitylene). The solution was stirred at room temperature in 0.5 dramvials, with the cap loosely screwed on. The progress of the reaction wasmonitored by aliquots taken at 10, 40, 110 and 400 minutes from theonset of the reaction. Aliquots were taken directly from the reactionmixture and added to an NMR tube, where they were quenched by moistCDCl₃. Z-selectivity was determined by integrating the resonancescorresponding to cis- and trans-7-tetradecene.

Crystallographic Details.

Low-temperature diffraction data (φ- and ω-scans) were collected on aBruker D8 three-circle diffractometer coupled to a Bruker-AXS Smart ApexCCD detector with graphite-monochromated Cu Kα radiation (λ=1.54178 Å)for the structures of compounds 3a and 3b and on a Bruker-AXS X8 KappaDuo diffractometer coupled to a Smart Apex2 CCD detector with Mo Kαradiation (λ=0.71073 Å) from an Incoatec IμS micro-source for thestructure of compound 5. The structures were solved by direct methodsusing SHELXS (Sheldrick, G. M., Acta Cryst. 1990, A46, 467-473) andrefined against F² on all data by full-matrix least squares withSHELXL-97 (Sheldrick, G. M., Acta Cryst. 2008, A64, 112-122) followingestablished refinement strategies (Müller, P. Crystallography Reviews2009, 15, 57-83). All non-hydrogen atoms were refined anisotropically.Except for hydrogen atoms on carbon atoms in direct contact with themetal (for details see below), all hydrogen atoms were included into themodel at geometrically calculated positions and refined using a ridingmodel. The isotropic displacement parameters of all hydrogen atoms wereconstrained to 1.2 times the U_(eq) value of the atoms they are linkedto (1.5 times for methyl groups). Details of the data quality, a summaryof the residual values of the refinements as well as all other pertinentparameters are listed in Tables S1 to S15.

Compound 3a crystallizes in the orthorhombic space group P2₁2₁2₁ withone molecule of 3a and one benzene molecule in the asymmetric unit.Coordinates for the hydrogen atom on C1, that is the carbon atomdirectly binding to the metal, were taken from the difference Fouriersynthesis. The hydrogen atoms were subsequently refined semi-freely withthe help of a distance restraint on the C—H-distance (target 0.95(2)Å).

TABLE 2 Crystal data and structure refinement for 3a. Identificationcode d10107 Empirical formula C₇₂ H₇₀ Mo N₄ O Formula weight 1103.26Temperature 100(2) K Wavelength 1.54178 Å Crystal system OrthorhombicSpace group P2₁2₁2₁ Unit cell dimensions a = 12.2807(2) Å α = 90°. b =20.2298(3) Å β = 90°. c = 23.4545(3) Å γ = 90°. Volume 5826.94(15) Å³ Z4 Density (calculated) 1.258 Mg/m³ Absorption coefficient 2.205 mm⁻¹F(000) 2320 Crystal size 0.20 × 0.20 × 0.10 mm³ Theta range for datacollection 2.88 to 70.04°. Index ranges −14 <= h <= 14, −24 <= k <= 24,−28 <= l <= 28 Reflections collected 119291 Independent reflections11008 [R_(int) = 0.0445] Completeness to theta = 70.04° 99.8% Absorptioncorrection Semi-empirical from equivalents Max. and min. transmission0.8097 and 0.6669 Refinement method Full-matrix least-squares on F²Data/restraints/parameters 11008/1/714 Goodness-of-fit on F² 1.059 FinalR indices [I > 2σ(I)] R1 = 0.0266, wR2 = 0.0693 R indices (all data) R1= 0.0274, wR2 = 0.0700 Absolute structure parameter −0.015(4) Largestdiff. peak and hole 0.891 and −0.348 e.Å⁻³

Compound 3b crystallizes in the monoclinic space group P2₁/c with onemolecule of 3b and one pentane molecule in the asymmetric unit.Coordinates for the hydrogen atom on C1, that is the carbon atomdirectly binding to the metal, were taken from the difference Fouriersynthesis. The hydrogen atoms were subsequently refined semi-freely withthe help of a distance restraint on the C—H-distance (target 0.95(2)Å).

TABLE 3 Crystal data and structure refinement for 3b. Identificationcode d10099 Empirical formula C₅₇ H₈₀ Mo N₄ O Formula weight 933.19Temperature 100(2) K Wavelength 1.54178 Å Crystal system MonoclinicSpace group P2₁/c Unit cell dimensions a = 19.1624(4) Å α = 90°. b =15.9182(3) Å β = 99.7440(10)°. c = 17.2741(3) Å γ = 90°. Volume5193.12(17) Å³ Z 4 Density (calculated) 1.194 Mg/m³ Absorptioncoefficient 2.370 mm⁻¹ F(000) 2000 Crystal size 0.45 × 0.30 × 0.10 mm³Theta range for data collection 2.34 to 69.32°. Index ranges −23 <= h <=23, −19 <= k <= 19, −20 <= l <= 20 Reflections collected 103056Independent reflections 9721 [R_(int) = 0.0314] Completeness to theta =69.32° 99.9% Absorption correction Semi-empirical from equivalents Max.and min. transmission 0.7975 and 0.4152 Refinement method Full-matrixleast-squares on F² Data/restraints/parameters 9721/1/585Goodness-of-fit on F² 1.026 Final R indices [I > 2σ(I)] R1 = 0.0251, wR2= 0.0645 R indices (all data) R1 = 0.0261, wR2 = 0.0653 Largest diff.peak and hole 0.506 and −0.457 e.Å⁻³

Crystals of 5 were grown from a mixture of toluene and pentane at −20°C. The compound crystallized in the triclinic space group P-1 with onemolecule in the asymmetric unit. Coordinates for the metallacyclehydrogen atoms were taken from the difference Fourier synthesis and thehydrogen atoms were subsequently refined semi-freely with the help of adistance restraint on the C—H distance (target 0.99(2)Å). The largestresidual election density was modeled as a second tungsten position andthe relative occupancy of the two components refined to 0.9367(12).Residual electron density proximal to the pyrrolide and alkoxide wasobserved in the difference Fourier synthesis but attempts to model astwo part disorder failed to achieve a stable refinement.

TABLE 4 Crystal data and structure refinement for 5 Identification codex8_12204 Empirical formula C57 H54 N4 O W Formula weight 994.89Temperature 100(2) K Wavelength 0.71073 Å Crystal system Triclinic Spacegroup P-1 Unit cell dimensions a = 13.2795(6) Å α = 62.0830(10)°. b =13.6061(6) Å β = 81.7030(10)°. c = 14.0913(7) Å γ = 86.4550(10)°. Volume2226.16(18) Å³ Z 2 Density (calculated) 1.484 Mg/m³ Absorptioncoefficient 2.641 mm⁻¹ F(000) 1012 Crystal size 0.30 × 0.23 × 0.19 mm³Theta range for data collection 1.55 to 31.59°. Index ranges −19 <= h <=19, −20 <= k <= 17, −20 <= l <= 20 Reflections collected 112060Independent reflections 14786 [R(int) = 0.0403] Completeness to theta =31.59° 99.1% Absorption correction Semi-empirical from equivalents Max.and min. transmission 0.6296 and 0.5006 Refinement method Full-matrixleast-squares on F² Data/restraints/parameters 14786/6/596Goodness-of-fit on F² 1.078 Final R indices [I > 2sigma(I)] R1 = 0.0246,wR2 = 0.0565 R indices (all data) R1 = 0.0290, wR2 = 0.0579 Largestdiff. peak and hole 1.132 and −0.650 e.Å⁻³

While several embodiments of the present invention have been describedand illustrated herein, those of ordinary skill in the art will readilyenvision a variety of other means and/or structures for performing thefunctions and/or obtaining the results and/or one or more of theadvantages described herein, and each of such variations and/ormodifications is deemed to be within the scope of the present invention.More generally, those skilled in the art will readily appreciate thatall parameters, dimensions, materials, and configurations describedherein are meant to be exemplary and that the actual parameters,dimensions, materials, and/or configurations will depend upon thespecific application or applications for which the teachings of thepresent invention is/are used. Those skilled in the art will recognize,or be able to ascertain using no more than routine experimentation, manyequivalents to the specific embodiments of the invention describedherein. It is, therefore, to be understood that the foregoingembodiments are presented by way of example only and that, within thescope of the appended claims and equivalents thereto, the invention maybe practiced otherwise than as specifically described and claimed. Thepresent invention is directed to each individual feature, system,article, material, kit, and/or method described herein. In addition, anycombination of two or more such features, systems, articles, materials,kits, and/or methods, if such features, systems, articles, materials,kits, and/or methods are not mutually inconsistent, is included withinthe scope of the present invention.

1. A compound of formula I:

wherein: M is molybdenum or tungsten; R¹ is an optionally substitutedgroup selected from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3heteroatoms independently selected from nitrogen, oxygen, or sulfur,phenyl, a 3-7 membered saturated or partially unsaturated carbocyclicring, an 8-10 membered bicyclic saturated, partially unsaturated or arylring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 3-7 memberedsaturated or partially unsaturated heterocyclic ring having 1-3heteroatoms independently selected from nitrogen, oxygen, or sulfur, a7-10 membered bicyclic saturated or partially unsaturated heterocyclicring having 1-5 heteroatoms independently selected from nitrogen,oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;each of R² and R³ is independently R′, —OR′, —SR′, —N(R′)₂, —OC(O)R′,—SOR′, —SO₂R′, —SO₂N(R′)₂, —C(O)N(R′)₂, —NR′C(O)R′, or —NR′SO₂R′; m is0-3; Ring B is an optionally substituted group selected from phenyl or a5-6 membered monocyclic heteroaryl ring having 1-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur; each of p and qis independently 0-4; each of Ring C and Ring D is independently anoptionally substituted 5-membered monocyclic heteroaryl ring having 1-4nitrogen atoms; each of R^(x), R^(y) and R^(z) is independently halogen,—OR′, —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)₂, —NR′SO₂R′,—NR′SO₂N(R′)₂, —NR′OR′, or an optionally substituted group selected fromC₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, phenyl, a 3-7membered saturated or partially unsaturated carbocyclic ring, an 8-10membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6membered monocyclic heteroaryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated orpartially unsaturated heterocyclic ring having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 7-10 memberedbicyclic saturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur; R⁴ is anoptionally substituted 5-membered monocyclic heteroaryl ring having 1-2nitrogen atoms; and each R′ is independently hydrogen or an optionallysubstituted group selected from C₁₋₆ aliphatic, phenyl, a 3-7 memberedsaturated or partially unsaturated carbocyclic ring, an 8-10 memberedbicyclic saturated, partially unsaturated or aryl ring, a 5-6 memberedmonocyclic heteroaryl ring having 1-4 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur, a 3-7 membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclicsaturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur; or: two R′groups on the same nitrogen atom are optionally taken together with thenitrogen atom to form an optionally substituted 3-8 membered, saturated,partially unsaturated, or aryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur; or a compound of formula II:

wherein: M is molybdenum or tungsten; R¹ is an optionally substitutedgroup selected from C₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3heteroatoms independently selected from nitrogen, oxygen, or sulfur,phenyl, a 3-7 membered saturated or partially unsaturated carbocyclicring, an 8-10 membered bicyclic saturated, partially unsaturated or arylring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 3-7 memberedsaturated or partially unsaturated heterocyclic ring having 1-3heteroatoms independently selected from nitrogen, oxygen, or sulfur, a7-10 membered bicyclic saturated or partially unsaturated heterocyclicring having 1-5 heteroatoms independently selected from nitrogen,oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;R^(2′) and R^(3′) are taken together with their intervening metal atomsto form an optionally substituted 3-8 membered saturated or partiallyunsaturated ring having, in addition to the intervening metal atom, 0-4heteroatoms independently selected from nitrogen, oxygen, or sulfur; mis 0-3; Ring B is an optionally substituted group selected from phenylor a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur; each of p and qis independently 0-4; each of Ring C and Ring D is independently anoptionally substituted 5-membered monocyclic heteroaryl ring having 1-4nitrogen atoms; each of R^(x), R^(y) and R^(z) is independently halogen,—OR′, —N(R′)₂, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)₂, —NR′SO₂R′,—NR′SO—N(R′)₂, —NR′OR′, or an optionally substituted group selected fromC₁₋₂₀ aliphatic, C₁₋₂₀ heteroaliphatic having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, phenyl, a 3-7membered saturated or partially unsaturated carbocyclic ring, an 8-10membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6membered monocyclic heteroaryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 3-7 membered saturated orpartially unsaturated heterocyclic ring having 1-3 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, a 7-10 memberedbicyclic saturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur; R⁴ is anoptionally substituted 5-membered monocyclic heteroaryl ring having 1-2nitrogen atoms; and each R′ is independently hydrogen or an optionallysubstituted group selected from C₁₋₆ aliphatic, phenyl, a 3-7 memberedsaturated or partially unsaturated carbocyclic ring, an 8-10 memberedbicyclic saturated, partially unsaturated or aryl ring, a 5-6 memberedmonocyclic heteroaryl ring having 1-4 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur, a 3-7 membered saturated or partiallyunsaturated heterocyclic ring having 1-3 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclicsaturated or partially unsaturated heterocyclic ring having 1-5heteroatoms independently selected from nitrogen, oxygen, or sulfur, oran 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatomsindependently selected from nitrogen, oxygen, or sulfur; or: two R′groups on the same nitrogen atom are optionally taken together with thenitrogen atom to form an optionally substituted 3-8 membered, saturated,partially unsaturated, or aryl ring having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, or sulfur.
 2. The compound of claim 1,wherein the compound is a compound of formula I, and one of R² and R³ ishydrogen and the other is optionally substituted C₁₋₂₀ aliphatic.
 3. Thecompound of claim 1, wherein the compound is a compound of formula II.4. The compound of claim 3, wherein the compound has the structure offormula II-a:


5. The compound of claim 1, wherein R¹ is optionally substituted C₁₋₂₀aliphatic.
 6. The compound of claim 1, wherein R¹ is optionallysubstituted phenyl.
 7. The compound of claim 1, wherein R¹ is selectedfrom


8. The compound of claim 1, wherein R⁴ is optionally substitutedpyrrolyl.
 9. A compound of formula III:

or a salt thereof.
 10. The compound of claim 1, wherein each of Ring Cand Ring D is independently optionally substituted pyrrolyl, imidazolylor pyrazolyl.
 11. The compound of claim 10, wherein each of Ring C andRing D is independently optionally substituted pyrrolyl.
 12. Thecompound of claim 11, wherein


13. The compound of claim 12, wherein


14. The compound of claim 1, wherein the compound is selected from


15. A method comprising: (a) providing a compound of claim 1; and (b)reacting a first unsaturated carbon-carbon bond and a second unsaturatedcarbon-carbon bond to produce a product comprising an unsaturatedcarbon-carbon bond.
 16. The method of claim 15, wherein the compound isa compound of claim
 14. 17. The method of claim 15, wherein each of theunsaturated carbon-carbon bonds is a carbon-carbon double bond.
 18. Themethod of claim 17, wherein the product comprises a carbon-carbon doublebond, and said carbon-carbon double bond is formed with Z-selectivity.19. The method of claim 18, wherein the Z-selectivity is greater thanabout 90%.
 20. The compound of claim 9, wherein the compound has thestructure of:

or a salt thereof.